JP2024512376A - Compounds useful in treating liver diseases - Google Patents

Abstract

The invention provides, for example, compounds of formulas (A)-(H) and (J)-(AA), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof. The invention further provides pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier or vehicle. The compounds and compositions disclosed herein can be used for various diseases and conditions, such as liver fibrosis, fatty liver disease, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). and kidney diseases such as acute kidney injury (AKI).

Description

1. CROSS REFERENCES TO RELATED APPLICATIONS This application is incorporated by reference no. 17/195,334 filed March 8, 2021, the entire contents of each of which is incorporated herein by reference to this application. 17/219,058 filed on March 31, 2021.

2. FIELD OF THE INVENTION The present invention relates to novel compounds, such as 2-(4-(3-hydroxy-3-(4-(methylthio)phenyl)prop-1-en-1-yl)-2,6-dimethylphenoxy) -2-Methylpropanoic acid (“Compound I”), 3-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)-3,5-dimethylphenyl)-1-(4-( methylthio)phenyl)prop-2-en-1-one (“Compound II”) and 3-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)-3,5-dimethylphenyl) -1-(4-(methylthio)phenyl)prop-2-en-1-ol ("Compound III"), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, and the like. , and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof. The present invention provides novel compounds described herein, such as Compound I, Compound II or Compound III, or pharmaceutically acceptable salts, solvates, esters, amides or prodrugs thereof. Compounds of Formulas (A) to (H) and (J) to (AA) or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, and a pharmaceutically acceptable carrier or vehicle. Further provided is a pharmaceutical composition comprising: The compounds and compositions disclosed herein are useful for treating conditions such as liver disease, such as liver fibrosis, fatty liver disease, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). Useful for treating or preventing.

3. Background Elevated levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides are associated with mixed dyslipidemia. Type IIb hyperlipidemia, a type of mixed lipid metabolism disorder, is characterized by elevated LDL-C and triglyceride levels, as well as increased levels of apolipoprotein B, very low-density lipoprotein cholesterol (VLDL-C), and medium-density lipoprotein cholesterol ( IDL), and small-dense low-density lipoprotein (LDL) levels.

Liver diseases such as non-alcoholic fatty liver disease (NAFLD) encompass a wide range of conditions ranging from relatively benign steatosis to the more severe non-alcoholic steatohepatitis (NASH), with the latter becoming more severe. If untreated, non-alcoholic steatohepatitis can lead to fibrosis, cirrhosis, liver failure or hepatocellular carcinoma. NAFLD and NASH can develop due to overproduction and accumulation of hepatic triglycerides. NAFLD is strongly associated with features of obesity, diabetes, dyslipidemia, hyperlipidemia and metabolic syndrome, including obesity, insulin resistance, type 2 diabetes and dyslipidemia. NASH can cause the liver to become swollen, inflamed, fibrous, damaged, and ultimately dysfunctional. NASH tends to develop in people who are overweight or obese, or who have diabetes, mixed dyslipidemia, high cholesterol or triglycerides, or inflammatory conditions. NASH is characterized by hepatocyte ballooning and liver inflammation that can lead to progression and irreversible changes to liver damage and scarring, similar to damage caused by heavy alcohol use. It will be done.

Hepatic steatosis and fibrosis can also be induced by drugs such as amiodarone, valproate, tamoxifen, methotrexate, and some chemotherapeutic and antiretroviral agents (Amacher, D.E., et al. Semin. Liver Dis., 2014, 34, 205). Drug-induced hepatic steatosis may be reversible and may be associated with drug accumulation within the liver.

NAFLD, NASH, hepatic steatosis or drug-induced hepatic steatosis can lead to metabolic complications, including increased liver enzymes, fibrosis, cirrhosis, hepatocellular carcinoma and liver failure. Liver failure is life-threatening, and therefore there is a need for the development of treatments to delay the onset of fatty liver, prevent its formation, or reverse the condition.

Peroxisome proliferator-activated receptors (PPARs) have been identified as targets for the treatment of cardiometabolic diseases, including diabetes, insulin resistance, dyslipidemia and liver disease, such as NAFLD and NASH. There are three types of PPAR: PPARα, PPARγ and PPARδ. Several PPAR agonists are on the market, including fenofibrate (PPARα agonist), bezafibrate (PPAR pan-agonist), pioglitazone (PPARγ agonist), and rosiglitazone (PPARγ agonist). Recently, PPAR agonists such as seladelpar (PPARδ agonist), ranifibranor (pan agonist) and elafibranor (dual PPARα/δ agonist) have been investigated to treat NASH and primary biliary cholangitis (PBC). However, several clinical trials involving such PPAR agonists have failed due to toxicity or failure to meet primary endpoints. For example, in a phase 3 trial in adults with NASH and fibrosis, elafibranor demonstrated no statistically significant effect on the primary endpoint of NASH resolution, without worsening fibrosis (ir .genfit.com/news-releases/news-release-details/genfit-announces-results-interim-analysis-resolve-it-phase-3).

PPARδ agonists have also been proposed as a treatment for acute kidney injury (AKI). For example, please refer to International Publication No. 2018/067857 pamphlet. AKI commonly occurs in ICU patients with an estimated incidence of >50% (Hoste et al., 2015, Intensive Care Med; 41:1411-1423). Furthermore, increased AKI severity is associated with increased mortality. Sepsis is a major cause of AKI, accounting for 70% to 45% of cases, with nearly 25% of sepsis having intra-abdominal origin (Seymour et al., 2016, JAMA, 315:762-774 ; Bagshaw et al., 2007, Clin J Am Soc Nephrol, 2:431-439). Ischemia/reperfusion injury (IRI) can lead to AKI and is a common complication in organ transplant recipients, with an incidence of 50-75% after lung and heart transplantation. Gueler et al., 2014, Transplantation 98:337-338). The PPARδ agonist ASP1128 (also known as MA-0217) (Astellas) is currently being investigated as a possible treatment for AKI after coronary artery bypass graft surgery and/or valve surgery ( ClinicalTrials.gov identifier NCT03941483). However, to date, no PPARδ agonist has been approved and marketed for the treatment of AKI.

There remains a need for new preventions and treatments for liver damage, kidney damage, and other conditions associated with PPARs.

4. SUMMARY OF THE INVENTION The present invention provides novel compounds and their use for treating a variety of disorders, including liver disorders such as NASH, kidney disorders such as AKI, and other conditions associated with PPARs. Without being bound by theory, the inventor believes that the clinical utility of PPAR agonists, such as elafibranor, is limited by their toxicity, and thus, in many cases, the dose cannot be increased sufficiently to reach an effective dose. thinking. The subject invention relates to derivatives of elafibranor and related compounds, and in WO 2011/020001, WO 2017/06246, WO 2017/180818 and WO 2018/067857. Novel compounds are provided, including derivatives of the described PPAR modulators. Without being bound by theory, the inventors believe that the compounds described herein can act as PPAR agonists and/or as PPAR agonist prodrugs, which may improve bioavailability following administration, and/or have advantageous properties that result in improved half-life, and/or safety, and/or efficacy, and/or improved therapeutic index. Thus, in particular, the compounds have an improved therapeutic index. The therapeutic index (TI) is the ratio comparing the dose at which a compound is toxic to the dose at which it is effective. One common measure of TI is TD ₅₀ /ED ₅₀ , where TD ₅₀ and ED ₅₀ are the toxic and effective doses, respectively, for 50% of the population. The higher the TI, the safer the compound. Compounds with low TI can be difficult to use in clinical practice and often require monitoring of plasma concentrations to prevent toxicity. One or more advantageous properties of the compounds of the present disclosure (elafibranor, or WO 2011/020001, WO 2011/020001, WO 2017/06246, WO 2017/180818 Comparison with known PPAR agonists, such as one or more PPAR agonists described in WO 2018/067857 and/or WO 2018/067857), for example, good solubility, good kinetics, better absorption, better PPAR receptor selectivity, reduced drug metabolism by cytochrome P450 or other enzymes such as reductases, reduced glucuronidation, reduced toxicity, or combinations thereof.

In various aspects, the invention provides compounds of formulas (A)-(H) and (J)-(AA), and pharmaceutically acceptable salts, solvates, esters, amides, and prodrugs thereof. provide.

In one aspect, the invention provides compounds of formula (A):

ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグを提供する
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＯＨ、－ＣＯＨ、－ＣＯＯＲ^３、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, where:
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COOH, -COH, -COOR ³ , -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4).

In another aspect, the invention also provides compounds of formula (B):

ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグを提供する
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＨ、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, where:
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COH, -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4).

The present invention provides 2-(4-(3-hydroxy-3-(4-(methylthio)phenyl)prop-1-en-1-yl)-2,6-dimethylphenoxy)-2-methylpropanoic acid (“ Compound I"), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, wherein Compound I has the structure:

を有する。

has.

The present invention also provides 3-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)-3,5-dimethylphenyl)-1-(4-(methylthio)phenyl)proper-2- En-1-one (“Compound II”), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, are provided, Compound II having the structure:

を有する。

has.

The present invention provides 3-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)-3,5-dimethylphenyl)-1-(4-(methylthio)phenyl)prop-2-ene -1-ol (“Compound III”), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, wherein Compound III has the structure:

を有する。

has.

In another aspect, the invention provides compounds of formula (C)

ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグを提供する
（式中、
Ｒ^１は、フェニル、ナフチル、ピリジル、チエニル、フリル、キノリルまたはベンゾチエニルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ｒ^２は、Ｃ_２～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、またはフェニル、ナフチルもしくはピリジルにより置換されているＣ_１～６アルキルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ａは、酸素、硫黄またはＮＲ^９であり、Ｒ^９は、水素またはＣ_１～８アルキルであり、
Ｘは、Ｃ_１～８アルキレン鎖であり、これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシもしくはヒドロキシルにより置換されており、０または１つの二重結合を有しており、
Ｙは、Ｃ（＝Ｏ）、Ｃ（＝Ｎ－ＯＲ^１０）、ＣＨ（ＯＲ^１１）、ＣＨ＝ＣＨ、Ｃ≡ＣまたはＣ（＝ＣＨ_２）であり、Ｒ^１０およびＲ^１１はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｒ^３、Ｒ^４およびＲ^５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルまたはピリジルであり、場合によりＲ^３、Ｒ^４およびＲ^５のうちの少なくとも１つは、水素ではなく、
Ｂは、ＣＨまたは窒素であり、
Ｚは、酸素または硫黄であり、
Ｒ^６およびＲ^７はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, where:
R ¹ is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, all of which are unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy , C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
R ² is C 1 substituted by C _2-8 alkyl, C _1-8 haloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, 3-7 membered _{cycloalkyl ~8} alkyl, or C _1-6 alkyl substituted by phenyl, naphthyl or pyridyl, either unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _{1-8 alkyl 8} alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
A is oxygen, sulfur or NR ⁹ and R ⁹ is hydrogen or C _1-8 alkyl;
X is a C _1-8 alkylene chain, which is unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy or hydroxyl and has 0 or 1 double bond; and
Y is C(=O), C(=N-OR ¹⁰ ), CH(OR ¹¹ ), CH=CH, C≡C or C(=CH ₂ ), and R ¹⁰ and R ¹¹ are each hydrogen or C _1-8 alkyl,
R ³ , R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _{2 ~8} alkynyl, halogen, _C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl, optionally at least one of R ³ , R ⁴ and R ⁵ is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In other aspects, the invention provides compounds of formulas (D) to (H) and (J) to (AA), and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof. provide.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

In a further aspect, the invention provides compounds of formulas (D) to (H) and (J) to (AA), e.g. salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

The present invention

を有する化合物、ならびに薬学的に許容されるその塩、溶媒和物、エステル、アミドおよびプロドラッグをさらに提供する。

and pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof.

Each compound of formulas (A) to (H) and (J) to (AA), each compound of compounds I, II, III, IV, V, Va, Vb, VI, VII and VIII, and items 5 to 7 Each compound described (including subparts thereof), or pharmaceutically acceptable salts, solvates, esters, amides and prodrugs thereof, is a "compound of the invention". Exemplary features of the compounds of the invention are described below in Section 5.2 and in Specific Embodiments 1-50 in Section 7.1 and Embodiments 1-209 in Section 7.2.

The invention also provides compositions (each composition being a "composition of the invention") comprising i) an effective amount of a compound of the invention, and ii) a pharmaceutically acceptable carrier or vehicle. . Exemplary features of the pharmaceutical compositions of the present disclosure are described below in Section 5.3, and specific embodiments 51-54 in Section 7.1, and embodiments 210-213 in Section 7.2. .

The present invention is applicable to liver disorders, lipid metabolism abnormalities, dyslipoproteinemia, renal diseases, disorders of glucose metabolism, disorders of lipid metabolism, disorders of carbohydrate (glucid) metabolism, cardiovascular diseases, vascular diseases, metabolic syndrome, metabolic Complications associated with the syndrome, PPAR-related disorders, sepsis, thrombotic disorders, obesity, diabetic nephropathy, diabetic retinopathy, atherosclerosis, pancreatitis, cerebrovascular disease, angiogenesis-related disorders, hypertension, cancer , inflammation, inflammatory diseases, neurodegenerative diseases, autoimmune diseases, oncological diseases, muscle atrophy, cholestasis, mitochondrial dysfunction, eye diseases, lysosomal storage diseases, kidney diseases (e.g. acute kidney injury) or erectile dysfunction. Further provided are methods of treatment or prevention comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention provides a method for treating or preventing dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, or dyslipidemia, which provides for a subject in need thereof, Further provided are methods comprising administering an effective amount of a compound of the invention or a composition of the invention.

The present invention detects abnormally high concentrations of high-low-density lipoprotein (LDL), apolipoprotein B (apoB), lipoprotein (a) (Lp(a)), and apolipoprotein (a) in the plasma or serum of a subject. or very low density lipoprotein (VLDL), or a method of preventing a subject from having abnormally high levels of the same, comprising administering to a subject in need thereof an effective amount of the present invention. Further provided are methods comprising administering a compound of the invention or a composition of the invention.

The present invention is a method of treating a subject with, or preventing a subject from having, an abnormally low concentration of high-density lipoprotein (HDL) in the subject's plasma or serum, comprising: Further provided are methods comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention provides a method for treating a subject having, or preventing a subject from having, an abnormally reduced or deficient lipoprotein lipase concentration or activity in the subject's plasma or serum, the subject in need thereof Further provided are methods comprising administering an effective amount of a compound of the invention or a composition of the invention.

The present invention provides a method for treating or preventing hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial combined hyperlipidemia. and administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention detects abnormally high concentrations of triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and non-high-density lipoprotein cholesterol (non-high-density lipoprotein cholesterol) in the plasma or serum of a subject. HDL-C), lipoprotein (a) (Lp(a)), apolipoprotein B, HDL/(VLDL+LDL) ratio, apolipoprotein C-II or apolipoprotein C-III, the method comprising: Further provided are methods comprising administering to a subject an effective amount of a compound of the invention or a composition of the invention.

The present invention is a method for improving abnormally low concentrations of high density lipoprotein (HDL)-related proteins, HDL-cholesterol, apolipoprotein AI or apolipoprotein E in the plasma or serum of a subject, the method comprising: Further provided are methods comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention is a method of promoting the clearance of triglycerides from the plasma or serum of a subject, the method comprising the step of administering to a subject in need thereof an effective amount of a compound of the present invention or a composition of the present invention. Further methods are provided.

The present invention provides a method for improving abnormally low glucose metabolism or abnormally low lipid metabolism in a subject, the method comprising administering an effective amount of a compound of the present invention or a composition of the present invention to a subject in need thereof. Further provided are methods comprising administering an agent.

The present invention provides a method of treating or preventing one or more of the symptoms of inflammation, systemic lupus erythematosus, lupus nephritis, or arthritis, comprising administering to a subject in need thereof an effective amount of a compound of the present invention or Further provided are methods comprising administering the composition.

The present invention further provides a method for reducing the fat content of meat in livestock, the method comprising administering to the livestock an effective amount of a compound of the invention or a composition of the invention.

The invention further provides a method of reducing the cholesterol content of poultry eggs, the method comprising administering to a species of poultry an effective amount of a compound of the invention or a composition of the invention.

Exemplary uses of the compounds and compositions of the disclosure are described in specific embodiments 55-163 in section 7.1 and specific embodiments 214-322 in section 7.2 below.

5. Detailed description of the invention 5.1. DEFINITIONS The term "about" when immediately followed by a numerical value means up to ±20% of that numerical value. For example, "about" a number means up to ±20% of this number, and in some embodiments up to ±19%, up to ±18%, up to ±17%, and in some embodiments up to ±16%. , maximum ±15%, maximum ±14%, maximum ±13%, maximum ±12%, maximum ±11%, maximum ±10%, maximum ±9%, maximum ±8%, maximum ±7% at maximum, ±6% at maximum, ±5% at maximum, ±4% at maximum, ±3% at maximum, ±2% at maximum, ±1% at maximum, less than ±1% at maximum, or means any other value or range of values in .

Throughout this specification, numerical ranges are presented in terms of certain specific quantities. These ranges include all subranges therein. Thus, the range "50-80" includes all possible ranges therein (eg, 51-79, 52-78, 53-77, 54-76, 55-75, 60-70, etc.). Additionally, all values within a given range may be endpoints of the range subsumed by them (e.g., the range 50-80 includes ranges that include endpoints 55-80, 50-75, etc.) .

The term "pharmaceutically acceptable salts" includes both acid and base addition salts. Pharmaceutically acceptable salts are prepared by reacting a compound of the invention, which functions as a base, with an inorganic or organic acid to form a salt such as hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, camphorsulfonic acid, oxalic acid. , maleic acid, succinic acid, citric acid, formic acid, hydrobromic acid, benzoic acid, tartaric acid, fumaric acid, salicylic acid, mandelic acid, carbonic acid, etc. Pharmaceutically acceptable salts can also be prepared by reacting a compound of the invention that functions as an acid with an inorganic or organic base to form a salt, such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, It can also be obtained by forming salts of copper, manganese, aluminum, ammonia, isopropylamine, trimethylamine, choline, betaine, etc. Inorganic bases can include, but are not limited to, calcium hydroxide, postassium hydroxide, sodium hydroxide, and sodium carbonate. Organic bases include, but are not limited to, naturally substituted amines, and isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, tromethamine, lysine, arginine, histidine, caffeine, procaine, Primary amines, secondary amines, tertiary amines, substituted amines, including cyclic amines such as hydrabamine, glucosamine, N-alkylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, etc. can include. Those skilled in the art will appreciate that pharmaceutically acceptable salts can be prepared by reacting a compound of the invention with a suitable inorganic or organic acid or base by any of several known methods. Let's be more aware of what we can do.

The term "solvate" refers to a solvated complex. Solvates may also be formed by solvation (a combination of solvent molecules and molecules or ions of a compound of the invention), or they may be aggregates comprising solute ions or molecules or solvent molecules. Can be done. The solvent may be water, in which case the solvate is a hydrate. Examples of hydrates include, but are not limited to, hemihydrate, monohydrate, dihydrate, trihydrate, hexahydrate, and the like. Solvates can be formed upon wetting, including through absorption of moisture. Pharmaceutically acceptable salts can also be solvates. When the solvate is obtained by crystallization from a solvent, the solvent may be an alcohol such as methanol or ethanol, an aldehyde, a ketone such as acetone, or an ester such as acetate.

The compounds of the invention may have one or more asymmetric centers and therefore may be enantiomers, racemates, diastereomers, other stereoisomers and mixtures thereof. The compounds of the present invention, whether or not specifically illustrated herein, include all such possible isomers (including geometric isomers), as well as racemic and optically pure forms thereof. including forms. Optically active (+) and (-), (R)- and (S)- or (D)- and (L)-isomers can be prepared using chiral synthons or chiral reagents; or can be resolved using conventional techniques such as chromatography and fractional crystallization. Conventional techniques for the preparation or isolation of individual enantiomers include chiral synthesis from suitable optically pure precursors or resolution of racemates using, for example, chiral high performance liquid chromatography (HPLC). included. Similarly, the compounds of the invention include all tautomeric forms.

The phrase "substantially free of its corresponding opposite enantiomer" means no more than about 10 mol%, in another embodiment, no more than about 5 mol%, in another embodiment, no more than about 2 mol%, another embodiment means having less than or equal to about 1 mol % of its corresponding opposite enantiomer, in another embodiment, less than or equal to about 0.5 mol %, and in another embodiment, less than or equal to about 0.1 mol %.

The phrase "substantially free of its corresponding opposite stereoisomer" means no more than about 10 mol%, in another embodiment, no more than about 5 mol%, in another embodiment, no more than about 2 mol%, another embodiment means having no more than about 1 mol% of its corresponding opposite stereoisomer, in another embodiment no more than about 0.5 mol%, and in another embodiment no more than about 0.1 mol%.

The phrase "substantially free of other olefinic configurations of its corresponding opposite" means up to about 10 mol%, in another embodiment, up to about 5 mol%, in another embodiment, up to about 2 mol%, another In embodiments, the olefin has no more than about 1 mol%, in another embodiment, no more than about 0.5 mol%, and in another embodiment, no more than about 0.1 mol% of other olefin configurations of its corresponding opposite. means.

"Effective amount" when used in conjunction with a compound of the present invention, when administered to a subject, alone or in conjunction with another pharmaceutically active agent, to treat or prevent a disorder or condition disclosed herein. means the amount of a compound of the invention that is effective for.

"Effective amount" when used in conjunction with another pharmaceutically active agent is an effective amount, alone or in combination with a compound of the invention, to treat or prevent a disorder or condition disclosed herein. Refers to the amount of other pharmaceutically active agents.

A "subject" is a human or non-human mammal, such as a cow, horse, cat, dog, rodent or non-human primate. Humans can be male or female, children, adolescents or adults. Women can be pre-menarchal or post-menopausal.

“Mammals” include humans, laboratory animals (e.g., mice, rats, rabbits, monkeys, dogs, etc.) and domestic pets (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits, etc.). animals, and non-domestic animals, including wild animals.

All weight percentages (i.e., "wt%" and "wt%" and w/w) referred to herein are relative to the total weight of the mixture or composition, as the case may be, unless otherwise indicated. .

"Alkyl" refers to a fully saturated straight or branched hydrocarbon chain having from 1 to 12 carbon atoms, as defined above, attached to the atoms by single bonds. Included are alkyls having a number of carbon atoms ranging from 1 to 12. Alkyl groups having 1 to 12 carbon atoms are C ₁ -C ₁₂ alkyl (alternatively designated as C _{1 -12} alkyl); alkyl groups having 1 to 10 carbon atoms are C 1 -C 12 alkyl; ₁ -C ₁₀ alkyl (alternatively designated as C _1-10 alkyl) and having 1 to 6 carbon atoms are C ₁ -C ₆ alkyl (alternatively designated as C _1-6 alkyl) and an alkyl group having 1 to 5 carbon atoms is C ₁ -C ₅ alkyl (alternatively expressed as C _1-5 alkyl). C ₁ -C ₅ alkyl includes C ₅ alkyl, C ₄ alkyl, C ₃ alkyl, C ₂ alkyl and C ₁ alkyl (ie, methyl). C ₁ -C ₆ alkyl includes all of the moieties listed above for C ₁ -C ₅ alkyl, but also includes C ₆ alkyl. C ₁ -C ₁₀ alkyl includes all of the moieties mentioned above for C ₁ -C ₅ alkyl and C ₁ -C ₆ alkyl, but also includes C ₇ , C ₈ , C ₉ and C ₁₀ alkyl. Similarly, C ₁ -C ₁₂ alkyl includes all of the moieties mentioned above, but also includes C ₁₁ and C ₁₂ alkyl. Non-limiting examples of C ₁ -C ₁₂ alkyl include methyl, ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, t -amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl and n-dodecyl. Unless stated otherwise, alkyl groups can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, alkyl groups are unsubstituted.

"Alkoxy" refers to RO, where R is alkyl.

"Alkenyl" refers to a straight or branched hydrocarbon chain having 2 to 12 carbon atoms and one or more carbon-carbon double bonds. Each alkenyl group is attached to an atom by a single bond. Included are alkenyl groups having a number of carbon atoms ranging from 2 to 12. Alkenyl groups having 2 to 12 carbon atoms are C ₂ -C ₁₂ alkenyl (alternatively designated as C _{2 -12} alkenyl); Alkenyl groups which are ₂ -C ₁₀ alkenyl (alternatively designated as C _2-10 alkenyl) and have 2 to 6 carbon atoms are C ₂ -C ₆ alkenyl (alternatively designated as C _2-6 alkenyl). and alkenyl groups having 2 to 5 carbon atoms include C ₂ -C ₅ alkenyl (alternatively represented as C _2-5 alkenyl). C ₂ -C ₅ alkenyl includes C ₅ alkenyl, C ₄ alkenyl, C ₃ alkenyl and C ₂ alkenyl. C ₂ -C ₆ alkenyl includes all of the moieties listed above for C ₂ -C ₅ alkenyl, but also includes C ₆ alkenyl. C ₂ -C ₁₀ alkenyl includes all of the moieties mentioned above for C ₂ -C ₅ alkenyl and C ₂ -C ₆ alkenyl, but also includes C ₇ , C ₈ , C ₉ and C ₁₀ alkenyl. Similarly, C ₂ -C ₁₂ alkenyl includes all of the moieties mentioned above, but also includes C ₁₁ and C ₁₂ alkenyl. Non-limiting examples of C ₂ -C ₁₂ alkenyl include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3 -Butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl , 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3 -nonenyl, 4-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 1-decenyl, 2-decenyl, 3-decenyl, 4-decenyl, 5-decenyl, 6-decenyl, 7-decenyl , 8-decenyl, 9-decenyl, 1-undecenyl, 2-undecenyl, 3-undecenyl, 4-undecenyl, 5-undecenyl, 6-undecenyl, 7-undecenyl, 8-undecenyl, 9-undecenyl, 10-undecenyl, 1 -dodecenyl, 2-dodecenyl, 3-dodecenyl, 4-dodecenyl, 5-dodecenyl, 6-dodecenyl, 7-dodecenyl, 8-dodecenyl, 9-dodecenyl, 10-dodecenyl and 11-dodecenyl. Unless stated otherwise, alkyl groups can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, alkenyl groups are unsubstituted.

"Alkynyl" refers to a straight or branched hydrocarbon chain radical having 2 to 12 carbon atoms and one or more carbon-carbon triple bonds. Each alkynyl group is attached to an atom by a single bond. Included are alkynyl groups having a number of carbon atoms ranging from 2 to 12. Alkynyl groups having 2 to 12 carbon atoms are C ₂ -C ₁₂ alkynyl (alternatively designated as C _{2 -12} alkynyl); Alkynyl groups having ₂ to 6 carbon atoms are C _{2 -C 10 alkynyl} (alternatively designated as C _2-6 alkynyl) and have _{2 to 6} carbon atoms. and an alkynyl group having 2 to 5 carbon atoms is C ₂ -C ₅ alkynyl (alternatively expressed as C _2-5 alkynyl). C ₂ -C ₅ alkynyl includes C ₅ alkynyl, C ₄ alkynyl, C ₃ alkynyl and C ₂ alkynyl. C ₂ -C ₆ alkynyl includes all of the moieties listed above for C ₂ -C ₅ alkynyl, but also includes C ₆ alkynyl. C ₂ -C ₁₀ alkynyl includes all of the moieties mentioned above for C ₂ -C ₅ alkynyl and C ₂ -C ₆ alkynyl, but also includes C ₇ , C ₈ , C ₉ and C ₁₀ alkynyl. Similarly, C ₂ -C ₁₂ alkynyl includes all of the moieties mentioned above, but also includes C ₁₁ and C ₁₂ alkynyl. Non-limiting examples of C ₂ -C ₁₂ alkenyl include ethynyl, propynyl, butynyl, pentynyl, and the like. Unless stated otherwise, alkyl groups can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, alkynyl groups are unsubstituted.

"Aryl" refers to a cyclic hydrocarbon ring system radical containing hydrogen, 6 to 18 carbon atoms, and at least one aromatic ring. Aryl radicals can be monocyclic, bicyclic, tricyclic or tetracyclic ring systems, including fused or bridged ring systems. Aryl radicals include, but are not limited to, aceantrylenyl, acenaphthylenyl, acephenanthrylenyl, anthracenyl, azulenyl, chrysenyl, fluoranthenyl, fluorenyl, as-indacenyl, s-indacenyl, indanyl, indenyl, naphthalenyl, phenalenyl. , phenanthrenyl, phenyl, pleiadenyl, pyrenyl, and triphenylenyl. Unless otherwise specified, aryl can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, aryl groups are unsubstituted.

"Cycloalkyl" refers to a non-aromatic monocyclic or polycyclic fully saturated hydrocarbon radical consisting of carbon and hydrogen atoms, preferably having from 3 to 20 carbon atoms. It can include fused or bridged ring systems having from 3 to 10 carbon atoms, which are attached to the atoms by single bonds. Monocyclic cycloalkyl radicals include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Polycyclic cycloalkyl radicals include, for example, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless stated otherwise, a cycloalkyl group can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, a cycloalkyl group is unsubstituted.

"Halo" or "halogen" represents chloro, fluoro, bromo or iodo.

"Haloalkyl" refers to an alkyl group in which one or more hydrogen atoms are replaced by a halogen. Examples of haloalkyl groups include trifluoromethyl ( _CF3 ), difluoromethyl ( _CF2H ), monofluoromethyl ( _CH2F ), pentafluoroethyl ( _{CF2CF3 )} , tetrafluoroethyl ( _CHFCF3 ), These include monofluoroethyl (CH ₂ CH ₂ F), trifluoroethyl (CH ₂ CF ₃ ), and tetrafluorotrifluoromethylethyl (CF(CF ₃ ) ₂ ).

"Haloalkoxy" refers to RO, where R is a haloalkyl group.

"Heteroaryl" means a 5- to 20-membered ring system radical containing a hydrogen atom, 1 to 13 carbon atoms, 1 to 6 nitrogen, oxygen, or sulfur heteroatoms, and at least one aromatic ring. Point. Heteroaryl radicals can be monocyclic, bicyclic, tricyclic or tetracyclic ring systems, which can include fused or bridged ring systems; A nitrogen, carbon or sulfur atom in a heteroaryl radical can optionally be oxidized, and a nitrogen atom can optionally be quaternized. Examples of heteroaryl include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1, 4] Dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxynyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophene), Benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophene, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, Isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl -1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl , tetrazolyl, triazinyl and thienyl. Unless stated otherwise, a heteroaryl group can be unsubstituted or substituted. In some embodiments, heteroaryl is unsubstituted.

"Heterocyclyl" refers to a 3- to 20-membered non-aromatic partially unsaturated radical or aromatic ring radical containing 2 to 12 carbon atoms and 1 to 6 nitrogen, oxygen, or sulfur heteroatoms. . Heterocyclyl includes heteroaryl as defined herein. Unless otherwise specified, a heterocyclyl radical can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, including fused, bridged and helical ring systems. a spiral ring system, the nitrogen, carbon or sulfur atoms in the heterocyclyl radical can optionally be oxidized, the nitrogen atom can optionally be quaternized, the heterocyclyl radical can be partially saturated or Can be fully saturated. Examples of heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl. , octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl , tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl and 1,1-dioxo-thiomorpholinyl. Unless stated otherwise, a heterocyclyl group can be unsubstituted or substituted with substituents disclosed herein. In some embodiments, a heterocyclyl group is unsubstituted.

As used herein, the symbol “

」または「

"or"

」（「結合（attachment bond）点」）は、２つの化学実体の間の結合点となる結合を表し、この一方は、結合点に結合していると図示され、この他方は、結合点に結合していると図示されていない。例えば、「

” (“attachment bond”) refers to a bond that serves as a point of attachment between two chemical entities, one of which is illustrated as being attached to the point of attachment, and the other of which is illustrated as being attached to the point of attachment. Not shown coupled. for example,"

」または「

"or"

」は、化学実体「ＸＹ」が、結合点を介して、別の化学実体に結合していることを示す。

” indicates that the chemical entity “XY” is bonded to another chemical entity via a bonding point.

5.2. Compounds of the invention 5.2.1. Compounds of Formula (A) In some embodiments, compounds of the invention are compounds of Formula (A):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＯＨ、－ＣＯＨ、－ＣＯＯＲ^３、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COOH, -COH, -COOR ³ , -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compound of formula (A) is racemic or a mixture of enantiomers or diastereomers. In some embodiments, the compound of formula (A) has the (Z) or (E) olefin isomeric configuration. In some embodiments, the hydroxyl-containing allylic carbon atom of the compound of formula (A) has (R)- or (S)-stereochemistry.

In some embodiments, the compound of formula (A) is the (Z)-isomer (or cis) and has the structure:

を有する。一部の実施形態では、式（（Ｚ）－Ａ）の化合物は、その対応する他のオレフィン立体配置（すなわち、（Ｅ）－異性体）を実質的に含まない。

has. In some embodiments, the compound of formula ((Z)-A) is substantially free of its corresponding other olefinic configuration (ie, the (E)-isomer).

In some embodiments, the compound of formula (A) is the (E)-isomer (or trans) and has the structure:

を有する。一部の実施形態では、式（（Ｅ）－Ａ）の化合物は、その対応する他のオレフィン立体配置（すなわち、（Ｚ）－異性体）を実質的に含まない。

has. In some embodiments, the compound of formula ((E)-A) is substantially free of its corresponding other olefinic configuration (ie, the (Z)-isomer).

In some embodiments, the compound of formula (A) has a hydroxyl-containing allylic carbon atom with an (R)-stereochemistry and the structure:

を有する。一部の実施形態では、式（（Ｒ）－Ａ）の化合物は、その対応する反対の立体異性体、すなわちそのヒドロキシル含有アリル炭素原子が（Ｓ）－立体化学を有する式（Ａ）の化合物を実質的に含まない。

has. In some embodiments, a compound of formula ((R)-A) is a compound of formula (A) in its corresponding opposite stereoisomer, i.e., a compound of formula (A) whose hydroxyl-containing allylic carbon atom has (S)-stereochemistry. Contains virtually no.

In some embodiments, the hydroxyl-containing allylic carbon atom of the compound of formula (A) has the (S)-stereochemistry and the structure:

を有する。一部の実施形態では、式（（Ｓ）－Ａ）の化合物は、その対応する反対の立体異性体、すなわちそのヒドロキシル含有アリル炭素原子が（Ｒ）－立体化学を有する式（Ａ）の化合物を実質的に含まない。

has. In some embodiments, a compound of formula ((S)-A) is a compound of formula (A) in its corresponding opposite stereoisomer, i.e., a compound of formula (A) whose hydroxyl-containing allylic carbon atom has an (R)-stereochemistry. Contains virtually no.

In some embodiments, the compound of formula (A) is the (Z)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (R)-stereochemistry and has the structure:

を有する。一部の実施形態では、式（（Ｚ）－（Ｒ）－Ａ）の化合物は、式（（Ｚ）－（Ｓ）－Ａ）、（（Ｅ）－（Ｒ）－Ａ）または（（Ｅ）－（Ｓ）－Ａ）の化合物を実質的に含まない。

has. In some embodiments, the compound of formula ((Z)-(R)-A) has the formula ((Z)-(S)-A), ((E)-(R)-A) or (( E)-(S)-A) Compound is not substantially contained.

In some embodiments, the compound of formula (A) is the (Z)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (S)-stereochemistry and has the structure:

を有する。一部の実施形態では、式（（Ｚ）－（Ｓ）－Ａ）の化合物は、式（（Ｚ）－（Ｒ）－Ａ）、（（Ｚ）－（Ｒ）－Ａ）または（（Ｚ）－（Ｓ）－Ａ）の化合物を実質的に含まない。

has. In some embodiments, the compound of formula ((Z)-(S)-A) has the formula ((Z)-(R)-A), ((Z)-(R)-A) or (( It does not substantially contain the compound Z)-(S)-A).

In some embodiments, the compound of formula (A) is the (E)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (R)-stereochemistry and the structure:

を有する。一部の実施形態では、式（（Ｅ）－（Ｒ）－Ａ）の化合物は、式（（Ｅ）－（Ｓ）－Ａ）、（（Ｚ）－（Ｒ）－Ａ）または（（Ｚ）－（Ｓ）－Ａ）の化合物を実質的に含まない。

has. In some embodiments, the compound of formula ((E)-(R)-A) has the formula ((E)-(S)-A), ((Z)-(R)-A) or (( It does not substantially contain the compound Z)-(S)-A).

In some embodiments, the compound of formula (A) is the (E)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (S)-stereochemistry and the structure:

を有する。一部の実施形態では、式（（Ｅ）－（Ｓ）－Ａ）の化合物は、式（（Ｅ）－（Ｒ）－Ａ）、（（Ｚ）－（Ｒ）－Ａ）または（（Ｚ）－（Ｓ）－Ａ）の化合物を実質的に含まない。

has. In some embodiments, the compound of formula ((E)-(S)-A) has the formula ((E)-(R)-A), ((Z)-(R)-A) or (( It does not substantially contain the compound Z)-(S)-A).

Formula (A), ((Z)-A), ((E)-A), ((R)-A), ((S)-A), ((E)-(R)-A), ( In some embodiments of the compounds (E)-(S)-A), ((Z)-(R)-A), or ((Z)-(S)-A), R ¹ and R ² are Each is independently -C ₁ -C ₆ alkyl. In some embodiments, R ¹ and R ² are each independently -C ₁ -C ₃ alkyl. In some embodiments, R ¹ and R ² are each independently methyl.

Formula (A), ((Z)-A), ((E)-A), ((R)-A), ((S)-A), ((E)-(R)-A), ( In some embodiments of the compounds (E)-(S)-A), ((Z)-(R)-A), or ((Z)-(S)-A), X is _-CH2 OH, -COOH, -COH or -COOR ³ or -COOCH ₂ CONR ⁴ R ⁵ . In some embodiments, X is -CH ₂ OH, -COOH, -COOR ³ , -COOCH ₂ CONR ⁴ R ⁵ . In some embodiments, X is -CH ₂ OH or -COOH.

Formula (A), ((Z)-A), ((E)-A), ((R)-A), ((S)-A), ((E)-(R)-A), ( In some embodiments of the compounds (E)-(S)-A), ((Z)-(R)-A), or ((Z)-(S)-A), R ³ is -C ₁ to C ₆ alkyl. In some embodiments, R ³ is methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, or t-butyl.

Formula (A), ((Z)-A), ((E)-A), ((R)-A), ((S)-A), ((E)-(R)-A), ( In some embodiments of the compounds (E)-(S)-A), ((Z)-(R)-A), or ((Z)-(S)-A), n is 0, 1 , 2 or 3. In some embodiments, n is 0, 1 or 2. In some embodiments, n is 0 or 1.

5.2.1.1. Compound I
In some embodiments, compounds of the invention have the structure:

を有する化合物Ｉ、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

In some embodiments, Compound I is racemic or a mixture of enantiomers. In some embodiments, Compound I has the (Z) or (E) olefinic isomeric configuration. In some embodiments, Compound I has a hydroxyl-containing allylic carbon atom with (R)- or (S)-stereochemistry.

In some embodiments, Compound I is the (Z)-isomer (or cis) and has the structure:

を有する。一部の実施形態では、化合物Ｉは、（Ｚ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｅ）－異性体）を実質的に含まない。

has. In some embodiments, Compound I is the (Z)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (E)-isomer).

In some embodiments, Compound I is the (E)-isomer (or trans) and has the structure:

を有する。一部の実施形態では、化合物Ｉは、（Ｅ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｚ）－異性体）を実質的に含まない。

has. In some embodiments, Compound I is the (E)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (Z)-isomer).

In some embodiments, Compound I has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物Ｉは、（Ｒ）－鏡像異性体を有するヒドロキシル含有アリル炭素原子を有しており、その対応する反対の鏡像異性体（すなわち、（Ｓ）－鏡像異性体）を実質的に含まない。

has. In some embodiments, Compound I has a hydroxyl-containing allylic carbon atom that has the (R)-enantiomer and its corresponding opposite enantiomer (i.e., the (S)-enantiomer). Contains virtually no.

In some embodiments, Compound I has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物Ｉは、（Ｓ）－鏡像異性体を有するヒドロキシル含有アリル炭素原子を有しており、その対応する反対の鏡像異性体（すなわち、（Ｒ）－鏡像異性体）を実質的に含まない。一部の実施形態では、化合物Ｉは、その（Ｒ）－鏡像異性体と（Ｓ）－鏡像異性体との非ラセミ混合物である。一部の実施形態では、非ラセミ混合物は、（Ｓ）－鏡像異性体に対して（Ｒ）－鏡像異性体を過剰に有する。一部の実施形態では、非ラセミ混合物は、（Ｒ）－鏡像異性体に対して（Ｓ）－鏡像異性体を過剰に有する。

has. In some embodiments, Compound I has a hydroxyl-containing allylic carbon atom that has a (S)-enantiomer and its corresponding opposite enantiomer (i.e., (R)-enantiomer) Contains virtually no. In some embodiments, Compound I is a non-racemic mixture of its (R)- and (S)-enantiomers. In some embodiments, the non-racemic mixture has an excess of the (R)-enantiomer over the (S)-enantiomer. In some embodiments, the non-racemic mixture has an excess of the (S)-enantiomer over the (R)-enantiomer.

In some embodiments, Compound I is the (Z)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｚ）－（Ｒ）－Ｉ）は、化合物（（Ｚ）－（Ｓ）－Ｉ）、（（Ｅ）－（Ｒ）－Ｉ）または（（Ｅ）－（Ｓ）－Ｉ）を実質的に含まない。

has. In some embodiments, the compound ((Z)-(R)-I) is the compound ((Z)-(S)-I), ((E)-(R)-I) or ((E) -(S)-I).

In some embodiments, Compound I is the (Z)-isomer and has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｚ）－（Ｓ）－Ｉ）は、化合物（（Ｚ）－（Ｒ）－Ｉ）、（（Ｅ）－（Ｒ）－Ｉ）または（（Ｅ）－（Ｓ）－Ｉ）を実質的に含まない。

has. In some embodiments, the compound ((Z)-(S)-I) is the compound ((Z)-(R)-I), ((E)-(R)-I) or ((E) -(S)-I).

In some embodiments, Compound I is the (E)-isomer (or trans) and has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｅ）－（Ｒ）－Ｉ）は、化合物（Ｅ）－（Ｓ）－Ｉ）、（（Ｚ）－（Ｒ）－Ｉ）または（（Ｚ）－（Ｓ）－Ｉ）を実質的に含まない。

has. In some embodiments, compound ((E)-(R)-I) is compound (E)-(S)-I), ((Z)-(R)-I) or ((Z)- It does not substantially contain (S)-I).

In some embodiments, Compound I is the (E)-isomer and has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and the structure:

を有する。一部の実施形態では、化合物（（Ｅ）－（Ｓ）－Ｉ）は、化合物（（Ｅ）－（Ｒ）－Ｉ）、（（Ｚ）－（Ｒ）－Ｉ）または（（Ｚ）－（Ｓ）－Ｉ）を実質的に含まない。

has. In some embodiments, the compound ((E)-(S)-I) is the compound ((E)-(R)-I), ((Z)-(R)-I) or ((Z) -(S)-I).

5.2.1.2. Compound III
In some embodiments, compounds of the invention have the structure:

を有する化合物ＩＩＩ、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

In some embodiments, Compound III is racemic or a mixture of enantiomers. In some embodiments, Compound III has the (Z) or (E) olefinic isomeric configuration. In some embodiments, Compound III has a hydroxyl-containing allylic carbon atom with (R)- or (S)-stereochemistry.

In some embodiments, Compound III is the (Z)-isomer (or cis) and has the structure:

を有する。一部の実施形態では、化合物ＩＩＩは、（Ｚ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｅ）－異性体）を実質的に含まない。

has. In some embodiments, Compound III is the (Z)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (E)-isomer).

In some embodiments, Compound III is the (E)-isomer (or trans) and has the structure:

を有する。一部の実施形態では、化合物ＩＩＩは、（Ｅ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｚ）－異性体）を実質的に含まない。

has. In some embodiments, Compound III is the (E)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (Z)-isomer).

In some embodiments, Compound III has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物ＩＩＩは、（Ｒ）－鏡像異性体を有するヒドロキシル含有アリル炭素原子を有しており、その対応する反対の鏡像異性体（すなわち、（Ｓ）－鏡像異性体）を実質的に含まない。

has. In some embodiments, Compound III has a hydroxyl-containing allylic carbon atom that has the (R)-enantiomer and its corresponding opposite enantiomer (i.e., the (S)-enantiomer). Contains virtually no.

In some embodiments, Compound III has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物ＩＩＩは、（Ｓ）－鏡像異性体を有するヒドロキシル含有アリル炭素原子を有しており、その対応する反対の鏡像異性体（すなわち、（Ｒ）－鏡像異性体）を実質的に含まない。一部の実施形態では、化合物ＩＩＩは、その（Ｒ）－鏡像異性体と（Ｓ）－鏡像異性体との非ラセミ混合物である。一部の実施形態では、非ラセミ混合物は、（Ｓ）－鏡像異性体に対して（Ｒ）－鏡像異性体を過剰に有する。一部の実施形態では、非ラセミ混合物は、（Ｒ）－鏡像異性体に対して（Ｓ）－鏡像異性体を過剰に有する。

has. In some embodiments, Compound III has a hydroxyl-containing allylic carbon atom that has a (S)-enantiomer and its corresponding opposite enantiomer (i.e., (R)-enantiomer) Contains virtually no. In some embodiments, Compound III is a non-racemic mixture of its (R)- and (S)-enantiomers. In some embodiments, the non-racemic mixture has an excess of the (R)-enantiomer over the (S)-enantiomer. In some embodiments, the non-racemic mixture has an excess of the (S)-enantiomer over the (R)-enantiomer.

In some embodiments, Compound III is the (Z)-isomer (or cis) and has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｚ）－（Ｒ）－ＩＩＩ）は、化合物（（Ｚ）－（Ｓ）－ＩＩＩ）、（（Ｅ）－（Ｒ）－ＩＩＩ）または（（Ｅ）－（Ｓ）－ＩＩＩ）を実質的に含まない。

has. In some embodiments, compound ((Z)-(R)-III) is compound ((Z)-(S)-III), ((E)-(R)-III), or ((E) -(S)-III).

In some embodiments, Compound III is the (Z)-isomer and has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｚ）－（Ｓ）－ＩＩＩ）は、化合物（（Ｚ）－（Ｒ）－ＩＩＩ）、（（Ｅ）－（Ｒ）－ＩＩＩ）または（（Ｅ）－（Ｓ）－ＩＩＩ）を実質的に含まない。

has. In some embodiments, compound ((Z)-(S)-III) is compound ((Z)-(R)-III), ((E)-(R)-III), or ((E) -(S)-III).

In some embodiments, Compound I is the (E)-isomer (or trans) and has a hydroxyl-containing allylic carbon atom with the (R)-enantiomer and has the structure:

を有する。一部の実施形態では、化合物（（Ｅ）－（Ｒ）－ＩＩＩ）は、化合物（（Ｅ）－（Ｓ）－ＩＩＩ）、（（Ｚ）－（Ｒ）－ＩＩＩ）または（（Ｚ）－（Ｓ）－ＩＩＩ）を実質的に含まない。

has. In some embodiments, compound ((E)-(R)-III) is compound ((E)-(S)-III), ((Z)-(R)-III), or ((Z) -(S)-III).

In some embodiments, Compound III is the (E)-isomer and has a hydroxyl-containing allylic carbon atom with the (S)-enantiomer and the structure:

を有する。一部の実施形態では、化合物（（Ｅ）－（Ｓ）－ＩＩＩ）は、化合物（（Ｅ）－（Ｒ）－ＩＩＩ）、（（Ｚ）－（Ｒ）－ＩＩＩ）または（（Ｚ）－（Ｓ）－ＩＩＩ）を実質的に含まない。

has. In some embodiments, compound ((E)-(S)-III) is compound ((E)-(R)-III), ((Z)-(R)-III), or ((Z) -(S)-III).

5.2.2. Compounds of Formula (B) In some embodiments, compounds of the invention are compounds of Formula (B):

または薬学的に許容されるその塩、溶媒和物エステル、アミドもしくはプロドラッグであり、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＨ、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate ester, amide or prodrug thereof;
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COH, -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である。

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4.

In some embodiments, the compound of formula (B) is racemic or a mixture of enantiomers. In some embodiments, the compound of formula (B) has the (Z) or (E) olefin isomeric configuration.

In some embodiments, the compound of formula (B) is the (Z)-isomer (or cis) and has the structure:

を有する。一部の実施形態では、式（Ｂ）の化合物は、（Ｚ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｅ）－異性体）を実質的に含まない。

has. In some embodiments, the compound of formula (B) is the (Z)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (E)-isomer).

In some embodiments, the compound of formula (B) is the (E)-isomer (or trans) and has the structure:

を有する。一部の実施形態では、式（Ｂ）の化合物は、（Ｅ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｚ）－異性体）を実質的に含まない。

has. In some embodiments, the compound of formula (B) is the (E)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (Z)-isomer).

In some embodiments of compounds of formula (B), R ¹ and R ² are each independently -C ₁ -C ₆ alkyl. In some embodiments, R ¹ and R ² are each independently -C ₁ -C ₃ alkyl. In some embodiments, R ¹ and R ² are each independently methyl.

In some embodiments of compounds of formula (B), X is -CH ₂ OH, -COH or -COOCH ₂ CONR ⁴ R ⁵ . In some embodiments, X is -CH ₂ OH.

In some embodiments of compounds of formula (B), R ³ is -C ₁ -C ₆ alkyl. In some embodiments, R ³ is methyl, ethyl, n-propyl, isopropyl, n-butyl, s-butyl, or t-butyl.

In some embodiments of compounds of formula (B), n is 0, 1, 2 or 3. In some embodiments, n is 0, 1 or 2. In some embodiments, n is 0 or 1.

5.2.2.1. Compound II
In some embodiments, compounds of the invention have the structure:

を有する化合物ＩＩ、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

In some embodiments, Compound II has the (Z) or (E) olefinic isomeric configuration.

In some embodiments, Compound II is the (Z)-isomer (or cis) and has the structure:

を有する。一部の実施形態では、化合物ＩＩは、（Ｚ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｅ）－異性体）を実質的に含まない。

has. In some embodiments, Compound II is the (Z)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (E)-isomer).

In some embodiments, Compound II is the (E)-isomer (or trans) and has the structure:

を有する。一部の実施形態では、化合物ＩＩは、（Ｅ）－異性体であり、その対応する他のオレフィン立体配置（すなわち、（Ｚ）－異性体）を実質的に含まない。

has. In some embodiments, Compound II is the (E)-isomer and is substantially free of its corresponding other olefinic configuration (ie, the (Z)-isomer).

5.2.3. Compounds of Formula (C) In some embodiments, compounds of the invention are compounds of Formula (C):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１は、フェニル、ナフチル、ピリジル、チエニル、フリル、キノリルまたはベンゾチエニルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ｒ^２は、Ｃ_２～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、またはフェニル、ナフチルもしくはピリジルにより置換されているＣ_１～６アルキルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ａは、酸素、硫黄またはＮＲ^９であり、Ｒ^９は、水素またはＣ_１～８アルキルであり、
Ｘは、Ｃ_１～８アルキレン鎖であり、これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシもしくはヒドロキシルにより置換されており、０または１つの二重結合を有しており、
Ｙは、Ｃ（＝Ｏ）、Ｃ（＝Ｎ－ＯＲ^１０）、ＣＨ（ＯＲ^１１）、ＣＨ＝ＣＨ、Ｃ≡ＣまたはＣ（＝ＣＨ_２）であり、Ｒ^１０およびＲ^１１はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｒ^３、Ｒ^４およびＲ^５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルまたはピリジルであり、場合によりＲ^３、Ｒ^４およびＲ^５のうちの少なくとも１つは、水素ではなく、
Ｂは、ＣＨまたは窒素であり、
Ｚは、酸素または硫黄であり、
Ｒ^６およびＲ^７はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, all of which are unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy , C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
R ² is C 1 substituted by C _2-8 alkyl, C _1-8 haloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, 3-7 membered _{cycloalkyl ~8} alkyl, or C _1-6 alkyl substituted by phenyl, naphthyl or pyridyl, either unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _{1-8 alkyl 8} alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
A is oxygen, sulfur or NR ⁹ and R ⁹ is hydrogen or C _1-8 alkyl;
X is a C _1-8 alkylene chain, which is unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy or hydroxyl, and has 0 or 1 double bond. and
Y is C(=O), C(=N-OR ¹⁰ ), CH(OR ¹¹ ), CH=CH, C≡C or C(=CH ₂ ), and R ¹⁰ and R ¹¹ are each hydrogen or C _1-8 alkyl,
R ³ , R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _{2 ~8} alkynyl, halogen, _C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl, optionally at least one of R ³ , R ⁴ and R ⁵ is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

Examples of alkyl groups having 1 to 8 carbon atoms in formula (C) include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl and pentyl.

Examples of alkyl groups having 1 to 8 carbon atoms and halogen substituents include methyl, ethyl, propyl, isopropyl, butyl and t, substituted by 1 to 3 halogens such as fluorine, chlorine and bromine. - Contains butyl. Examples include trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl and 2-fluoroethyl.

Examples of alkoxy groups having 1 to 8 carbon atoms include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and pentyloxy.

Examples of alkoxy groups having 1 to 8 carbon atoms and halogen substituents include methoxy, ethoxy, propoxy, iso, substituted by 1 to 3 halogen atoms, such as fluorine, chlorine or bromine. Includes propoxy, butoxy and t-butoxy groups. Includes trifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy and 2-fluoroethoxy.

Examples of alkenyl groups having 2 to 8 carbon atoms include vinyl and allyl.

Examples of alkynyl groups having 2 to 8 carbon atoms include propargyl.

Examples of 3- to 7-membered cycloalkyl groups include cyclohexyl and cyclopentyl.

Examples of alkyl groups having 1 to 8 carbon atoms and 3 to 7 membered cycloalkyl substituents include cyclohexylmethyl and cyclopentylmethyl.

Compounds of formula (C) can exist in the form of geometric isomers, such as cis and trans, as well as optical isomers. These isomers are included in the provided compounds. Additionally, the provided compounds can be in the form of pharmaceutically acceptable salts, such as alkali metal salts, eg, sodium or potassium salts.

In some embodiments, R ^X is CH ₂ OH, COH or COOCH ₂ CONR ⁴ R ⁵ . In other embodiments, R ^X is CH ₂ OH.

In some embodiments, the compound of formula (C) is

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

In some embodiments, the compound of formula (C) is a compound shown in Table 1, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.4. Compounds of Formula (D) In some embodiments, compounds of the invention are compounds of Formula (D):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、水素、ハロゲン、ニトロ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、場合により置換されているＣ_６～１０アリール、Ｃ_６～１０アリール部分およびＣ_１～８アルキル部分を有するアリールアルキル基、Ｃ_１～８アルキル基を有する複素環式基または複素環式アルキル基であり、
Ｒ^３、Ｒ^４およびＲ^５は出現ごとに、独立して、水素またはＣ_１～８アルキルであり、
Ａは、酸素原子、硫黄原子またはＮＲ^３であり、
Ｘ^１、Ｘ^２およびＺはそれぞれ、独立して、Ｃ（＝Ｏ）、Ｃ（＝Ｏ）ＮＨ、Ｃ（＝Ｎ－ＯＲ^４）、ＣＨ（ＯＲ^５）、ＮＨ（Ｃ＝Ｏ）、ＮＨＳＯ_２、ＳＯ_２ＮＨ、ＣＨ＝ＣＨ、Ｃ≡Ｃまたは結合であり、
Ｙは、Ｃ_１～８アルキレンであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently hydrogen, halogen, nitro, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1-3 halogens, 1-3 halogens. C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 alkyl substituted by 3-7 membered cycloalkyl, optionally substituted a C _6-10 aryl, an arylalkyl group having a C _6-10 aryl moiety and a C _1-8 alkyl moiety, a heterocyclic group or a heterocyclic alkyl group having a C _1-8 alkyl group,
R ³ , R ⁴ and R ⁵ at each occurrence are independently hydrogen or C _1-8 alkyl;
A is an oxygen atom, a sulfur atom or ^NR3 ,
X ¹ , X ² and Z are each independently C(=O), C(=O)NH, C(=N-OR ⁴ ), CH(OR ⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH=CH, C≡C or a bond,
Y is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

Examples of halogen atoms for R ¹ and R ² include fluorine, chlorine and bromine.

Examples of alkyl groups having 1 to 8 carbon atoms for R ¹ , R ² , R ³ , R ⁴ and R ⁵ include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl and pentyl. is included.

Examples of alkoxy groups having 1 to 8 carbon atoms for R ¹ and R ² include methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, t-butyloxy and pentyloxy.

Examples of alkyl groups having 1 to 8 carbon atoms with 1 to 3 halogen substituents in the case of R ¹ and R ² include chloromethyl, fluoromethyl, bromomethyl, chloroethyl, 2-fluoroethyl and Contains trifluoromethyl.

Examples of alkoxy groups having 1 to 8 carbon atoms with 1 to 3 halogen substituents in the case of R ¹ and R ² include chloromethoxy, fluoromethoxy, bromomethoxy, 2-chloroethoxy, 2 - Includes fluoroethoxy and trifluoroethoxy.

Examples of alkenyl groups having 2 to 8 carbon atoms for R ¹ and R ² include vinyl or allyl. An alkynyl group having 2 to 8 carbon atoms can be, for example, propargyl. A cycloalkyl group having 3 to 7 carbon atoms can be, for example, cyclohexyl or cyclopentyl. An alkyl group having a 3- to 7-membered cycloalkyl substituent can be, for example, cyclohexylmethyl or cyclopentylmethyl.

The aryl group in the case of an aryl group optionally bearing substituents in the case of R ¹ and R ² can be, for example, phenyl or naphthyl.

Examples of optionally substituted arylalkyl groups include benzyl and phenethyl.

Examples of heterocyclic groups in the case of heterocyclic groups optionally carrying substituents include 5- to 7-membered cyclic groups having 1 to 4 ring-forming heteroatoms such as nitrogen, oxygen and sulfur. It will be done. For example, pyridyl, thienyl and furyl may be included. Additionally, benzene rings fused to heterocyclic groups, such as quinolyl or benzothienyl, may be included.

Heterocyclic rings optionally bearing substituents - Examples of heterocyclic groups in the case of alkyl groups (the alkyl moiety has 1 to 8 carbon atoms) It can be the same as described earlier in this specification. Alkyl groups preferably have 1 to 3 carbon atoms.

Aryl radicals optionally bearing substituents, arylalkyl radicals optionally bearing substituents (the aryl part has 6 to 10 carbon atoms and the alkyl part has 1 to 8 carbon atoms), substituted Substituents for the substituents of heterocyclic groups optionally bearing groups and of heterocyclic ring-alkyl groups optionally bearing substituents (the alkyl moiety having 1 to 8 carbon atoms) include halogen atoms ( chlorine, bromine or fluorine), nitro, hydroxyl, amino, alkylamino groups having 1 to 8 carbon atoms (such as methylamino or ethylamino), dialkylamino groups having 2 to 10 carbon atoms (such as dimethylamino ), alkyl groups having 1 to 8 carbon atoms (such as methyl, ethyl, propyl, isopropyl or butyl), alkoxy groups having 1 to 8 carbon atoms (such as methoxy, ethoxy, propoxy, isopropoxy or butoxy) ), alkyl groups having 1 to 8 carbon atoms with 1 to 3 halogen substituents (such as chloromethyl, fluoromethyl, bromomethyl, 2-chloroethyl, 2-fluoroethyl or trifluoromethyl), 1 to 3 halogen substituents; 2 to 8 alkoxy groups having 1 to 8 carbon atoms (such as chloromethoxy, fluoromethoxy, bromomethoxy, 2-chloroethoxy, 2-fluoroethoxy or trifluoromethoxy) with 3 halogen substituents alkyenyl groups with 2 to 8 carbon atoms (such as vinyl or allyl), alkynyl groups with 2 to 8 carbon atoms (such as propargyl), cycloalkyl groups with 3 to 7 carbon atoms (such as cyclohexyl or cyclopentyl) ), an alkyl group having a cycloalkyl group of 3 to 7 carbon atoms (such as cyclohexylmethyl or cyclopentylmethyl), phenyl, or pyridyl.

In some embodiments, the compound of formula (D) is a compound shown in Table 2, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.5. Compounds of Formula (E) In some embodiments, compounds of the invention are compounds of Formula (E):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１１およびＲ^１２は、それぞれ、独立して、水素、ハロゲン、ニトロ、ヒドロキシル、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル基、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、あるいはフェニル、ナフチル、ベンジル、フェネチル、ピリジル、チエニル、フリル、キノリルまたはベンゾチエニル基（これらは、ハロゲン原子、ニトロ、ヒドロキシル、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル基、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル基、フェニルまたはピリジルである置換基を場合により有する）であり、
Ｘ^１およびＺ^１はそれぞれ、独立して、Ｃ（＝Ｏ）、Ｃ（＝Ｏ）ＮＨ、Ｃ（＝Ｎ－ＯＲ^１４）、ＣＨ（ＯＲ^１５）、ＮＨ（Ｃ＝Ｏ）、ＮＨＳＯ_２、ＳＯ_２ＮＨ、ＣＨ＝ＣＨ、Ｃ≡Ｃまたは結合であり、Ｒ^１４およびＲ^１５はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｙ^１は、Ｃ_１～８アルキレンであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹² are each independently hydrogen, halogen, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl group having 1 to 3 halogens, C _1-8 haloalkoxy group having 1 to 3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 having 3-7 membered cycloalkyl substituent ₈ alkyl, or phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl group (these are halogen atoms, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, 1- C _1-8 haloalkyl having 3 halogens, C _1-8 haloalkoxy having 1-3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl group, 3- a C _1-8 alkyl group with a 7-membered cycloalkyl substituent, optionally with a substituent that is phenyl or pyridyl),
X ¹ and Z ¹ are each independently C(=O), C(=O)NH, C(=N-OR ¹⁴ ), CH(OR ¹⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH═CH, C≡C or a bond, R ¹⁴ and R ¹⁵ are each hydrogen or C _1-8 alkyl,
Y ¹ is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, halogen atoms, alkoxy groups having 1 to 8 carbon atoms, 1 to 8 carbon atoms with 1 to 3 halogen substituents for R ¹¹ and R ¹² an alkyl group having 1 to 3 halogen substituents, an alkoxy group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkynyl group having 2 to 8 carbon atoms; , a cycloalkyl group having 3 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an alkyl group having 1 to 8 carbon atoms, R ¹ and R of formula (D) In the case of ² , a halogen atom, an alkoxy group, an alkyl group having 1 to 8 carbon atoms having a halogen substituent, an alkoxy group having 1 to 8 carbon atoms having a halogen substituent, alkenyl, alkynyl , cycloalkyl groups and cycloalkyl groups of 3 to 7 carbon atoms may be as described with respect to alkyl groups with 1 to 8 carbon atoms.

In some embodiments, the alkyl group having 1 to 8 carbon atoms for R ¹¹ , R ¹² , R ¹⁴ and R ¹⁵ is R ¹ , R ² , R ³ , R ⁴ of formula (D) and R 5 can be an alkyl group as described for R ⁵ .

When R ¹¹ or R ¹² is phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl, or benzothienyl, these rings are, in some embodiments, free of such substituents, halogen atoms ( chlorine, bromine or fluorine), nitro, hydroxyl, amino, alkylamino groups having 1 to 8 carbon atoms (such as methylamino or ethylamino), dialkylamino groups having 2 to 10 carbon atoms (such as dimethylamino ), alkyl groups having 1 to 8 carbon atoms (such as methyl, ethyl, propyl, isopropyl or butyl), alkoxy groups having 1 to 8 carbon atoms (such as methoxy, ethoxy, propoxy, isopropoxy or butoxy) ), alkyl groups having 1 to 8 carbon atoms with 1 to 3 halogen substituents (such as chloromethyl, fluoromethyl, bromomethyl, 2-chloroethyl, 2-fluoroethyl or trifluoromethyl), 1 to 3 halogen substituents; 2 to 8 alkoxy groups having 1 to 8 carbon atoms (such as chloromethoxy, fluoromethoxy, bromomethoxy, 2-chloroethoxy, 2-fluoroethoxy or trifluoromethoxy) with 3 halogen substituents alkenyl groups with 2 to 8 carbon atoms (such as vinyl or allyl), cycloalkyl groups with 3 to 7 carbon atoms (such as cyclohexyl or cyclopentyl), 3 Alkyl groups with cycloalkyl groups of up to 7 carbon atoms (such as cyclohexylmethyl or cyclopentylmethyl), phenyl or pyridyl can have.

The provided compounds may be stereoisomers, such as cis or trans, or optical isomers. These isomers are included in the present invention.

The provided compounds include pharmaceutically acceptable salts such as alkali metal salts, eg, sodium or potassium salts. Additionally, the provided compounds can be in the form of pharmaceutically acceptable salts such as alkali metal salts, such as sodium and potassium salts.

In some embodiments, the compound of formula (E) is a compound shown in Table 3, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.6. Compounds of Formula (F) In some embodiments, compounds of the invention are compounds of Formula (F):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ａは、Ｏ、ＳまたはＮＲ^７であり、Ｒ７は、水素またはＣ_１～８アルキルであり、
Ｂ^１は、ＣＷまたはＮであり、Ｗは、水素または結合であり、Ｂ^２は、Ｏ、ＳまたはＮＲ^８であり、Ｒ^８は、水素またはＣ_１～８アルキルであり、
Ｘ^１およびＸ^２はそれぞれ、Ｏ、Ｓ、ＮＨ、ＮＨＣ（＝Ｏ）、Ｃ（＝Ｏ）、Ｃ（＝Ｎ－ＯＲ^９）、ＣＨ（ＯＲ^１０）、Ｃ＝Ｃ、Ｃ≡Ｃまたは結合であり、Ｒ^９およびＲ^１０はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｙは、Ｃ_１～８アルキレンであり、これは、無置換であるか、またはＣ_１～８アルキル、もしくは１～３個のハロゲンを有するＣ_１～８ハロアルキルにより置換されており、
Ｚは、ＮＨ、ＯまたはＳであり、
Ｒ^１は、アリール（これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、ヒドロキシル、ニトロ、アミノ、フェニル、ピリジルまたはハロゲンにより置換されている）、または１～３個のヘテロ原子を含む５～８員の環を有する複素環式基（ヘテロ原子はそれぞれ、独立して、窒素、酸素または硫黄であり、他の原子は炭素である）であり、場合により、ベンゼン環は、複素環式環と縮合しており、
Ｒ^２は、Ｃ_２～８アルキル、１～３個のハロゲンを有するＣ_１～８ハロアルキル、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、アリール（これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、ヒドロキシル、ニトロ、アミノ、フェニル、ピリジルもしくはハロゲンにより置換されている）により置換されているＣ_１～４アルキル、または１～３個のヘテロ原子（これらはそれぞれ、独立して、窒素、酸素または硫黄である）を有する５～８員の環を有する複素環式基により置換されているＣ_１～４アルキルであり、
Ｒ^３は、ハロゲン、トリフルオロメチル、Ｃ_１～８アルキル、Ｃ_２～８アルケニルまたはＣ_２～８アルキニルであり、
Ｒ^４およびＲ^５はそれぞれ、水素、Ｃ_１～８アルキルまたは１～３個のハロゲンを有するＣ_１～８ハロアルキルであり、
ＺおよびＲ^３はそれぞれ、ベンゼン環に結合しており、Ｘ^２は、ベンゼン環に結合しておらず、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is O, S or ^NR7 , R7 is hydrogen or _C1-8 alkyl,
B ¹ is CW or N, W is hydrogen or a bond, B ² is O, S or NR ⁸ , R ⁸ is hydrogen or C _1-8 alkyl,
X ¹ and X ² are each O, S, NH, NHC (=O), C (=O), C (=N-OR ⁹ ), CH (OR ¹⁰ ), C=C, C≡C or a bond and R ⁹ and R ¹⁰ are each hydrogen or C _1-8 alkyl,
Y is C _1-8 alkylene, which is unsubstituted or substituted with C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z is NH, O or S;
R ¹ is aryl (which is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) or a heterocyclic group having a 5- to 8-membered ring containing 1 to 3 heteroatoms, each heteroatom being independently nitrogen, oxygen, or sulfur; the other atoms are carbon), and optionally the benzene ring is fused with a heterocyclic ring;
R ² is C _2-8 alkyl, C _1-8 haloalkyl having 1-3 halogens, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, aryl (this is an unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl with 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) C _1-4 alkyl, or a heterocyclic group having a 5- to 8-membered ring having 1 to 3 heteroatoms, each of which is independently nitrogen, oxygen, or sulfur; is C _1-4 alkyl,
R ³ is halogen, trifluoromethyl, C _1-8 alkyl, C _2-8 alkenyl or C _2-8 alkynyl;
R ⁴ and R ⁵ are each hydrogen, C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z and R ³ are each bonded to a benzene ring, X ² is not bonded to a benzene ring,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In formula (F), R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , a substituent on the alkylene chain of Y, a substituent on the aryl and heterocyclic group of R ³ , substituents for alkyl groups substituted by aryl in R ² , and substituents for alkyl groups substituted by heterocyclic groups in R ² , in some embodiments, have from 1 to 8 carbon atoms. It can be an alkyl group having the following. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.

In some embodiments, R ² can be an alkyl group having 2-8 carbon atoms. Examples of alkyl groups include ethyl, propyl, iso-propyl, butyl, isobutyl, t-butyl, pentyl and hexyl.

In some embodiments, R ² , R ⁴ , R ⁵ , a substituent on an alkylene chain of Y, a substituent on an aryl or heterocyclic group of R ¹ , a substituent of an alkyl group substituted by an aryl of R ² The substituents of the group and the alkyl group substituted by the heterocyclic group of R ² can be an alkyl group having 1 to 8 carbon atoms, substituted by 1 to 3 halogens. . Examples of haloalkyl groups include methyl, ethyl, propyl, isopropyl, butyl and t-butyl substituted with 1 to 3 halogens such as fluorine, chlorine and bromine. In some embodiments, the group is trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl or 2-fluoroethyl.

In some embodiments, R ² and R ³ can be alkenyl groups having 2-8 carbon atoms. Examples of alkenyl groups include vinyl and allyl. R ² and R ³ can be alkynyl groups having 2 to 8 carbon atoms. Examples of alkynyl groups include propargyl.

In some embodiments, R ³ can be a halogen atom. Examples of halogen atoms include fluorine, chlorine and bromine.

In some embodiments, R ² can be a cycloalkyl group having 3 to 7 carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclopentyl and cyclohexyl.

In some embodiments, a substituent for an aryl or heterocyclic group at R ¹ , a substituent for an alkyl group substituted by an aryl at R ² , and an alkyl group substituted by a heterocyclic group at R ² The substituents can be alkoxy groups having 1 to 8 carbon atoms. Examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy and hexyloxy.

In some embodiments, the aryl portion of R ¹ and the alkyl-substituted aryl of R ² can be an aryl group. Examples of aryl groups include phenyl and naphthyl. The substituent for the alkyl group of R ¹ and R ² can be a heterocyclic group having a 5- to 8-membered ring. Examples of heterocyclic groups include pyridyl, thienyl, furyl, thiazolyl and quinolyl.

In some embodiments, R ¹ can be a heterocyclic group having a 5-8 membered ring containing 1-3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; Other atoms consist of carbon. Benzene rings can be fused with heterocyclic rings. Examples of fused rings include quinoline rings and benzothiophene rings.

In some embodiments, Y can be an alkylene chain having 1-8 carbon atoms. Examples of alkylene chains include methylene and ethylene.

In some embodiments, R ³ can be 1-3 groups. In some embodiments, two or three groups of R ³ can be different from each other.

In some embodiments, R6 can be an alkyl group having 1-8 carbon atoms that is substituted with amino. Examples of aminoalkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl, which are substituted with amino groups such as piperidino, pyrrolidino, dimethylamino and diethylamino. There is.

In some embodiments, compounds of formula (F) can be in the form of pharmaceutically acceptable salts, such as alkali metal salts, such as sodium and potassium salts.

In some embodiments, the compound of formula (F) is a compound shown in Table 4, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.7. Compounds of Formula (G), (H) and (J) In some embodiments, compounds of the invention include compounds of Formula (G):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１およびＲ^４はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２は、水素であり、
Ｒ^３は、Ｃ_１～８アルキルであるか、またはＲ^３は、Ｒ^２と一緒になって、＝Ｏまたは＝Ｃ（Ｒ^７）（Ｒ^８）を形成し、Ｒ^７およびＲ^８はそれぞれ、同じであるか、または異なっており、水素またはＣ_１～８アルキルであり、
Ｒ^５およびＲ^６はそれぞれ、同じであるか、または異なっており、水素原子、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
ＸおよびＹは、同じであるか、または異なっており、それぞれ、ＣＨまたはＮを表し、
Ｚは、酸素または硫黄であり、
Ａは、ピラゾール、チオフェン、フランまたはピロールである５員の複素環式基であり、複素環式基は、無置換であるか、あるいはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基により置換されているＣ_１～８アルキル基、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式基である置換基を有するＣ_１～８アルキルにより置換されており、
Ｂは、Ｃ_１～８アルキレン鎖であり、これは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキルもしくはＣ_１～８ハロアルコキシにより置換されており、アルキレン基は、アルキレン基が、２～６個の炭素原子を有する場合、二重結合を場合により有しており、
ｑは、０、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ⁴ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ² is hydrogen;
R ³ is C _1-8 alkyl, or R ³ together with R ² forms =O or =C(R ⁷ )(R ⁸ ), and R ⁷ and R ⁸ are each , are the same or different and are hydrogen or C _1-8 alkyl,
R ⁵ and R ⁶ are each the same or different and are a hydrogen atom, C _1-8 alkyl, C _1-8 haloalkyl,
X and Y are the same or different and represent CH or N, respectively;
Z is oxygen or sulfur;
A is a 5-membered heterocyclic group which is pyrazole, thiophene, furan or pyrrole, and the heterocyclic group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl group substituted by a 3-7 membered cycloalkyl group, C _1-8 haloalkyl, C _1-8 haloalkoxy, A substituent that is a C _6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a 5- or 6-membered heterocyclic group substituted with C _1-8 alkyl having
B is a C _1-8 alkylene chain, which is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C Substituted by _1-8 alkoxy, halogen, C _1-8 haloalkyl or C _1-8 haloalkoxy, the alkylene group may optionally contain a double bond if the alkylene group has 2-6 carbon atoms. has,
q is 0, 1, 2, 3, 4 or 5,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (H):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１１およびＲ^１３はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^１２は、水素、Ｃ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^１４およびＲ^１５は、同じであるか、または異なっており、それぞれ、水素原子、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘ^１は、ＣＨまたはＮであり、
Ｚ^１は、酸素または硫黄であり、
Ｗ^１は、結合ａが存在する場合、酸素またはＣＨ_２であり、結合ａが存在しない場合、ＯＨであり、
ｑは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ¹² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ¹⁴ and R ¹⁵ are the same or different and each is a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ¹ is CH or N,
Z ¹ is oxygen or sulfur;
W ¹ is oxygen or CH ₂ when bond a is present, and OH when bond a is absent;
q is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (J):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^２１およびＲ^２３はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２２は、水素、Ｃ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２４およびＲ^２５は、同じであるか、または異なっており、それぞれ、水素原子、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘ^２は、ＣＨまたはＮであり、
Ｚ^２は、酸素または硫黄であり、
Ｗ^２は、結合ａが存在する場合、酸素またはＣＨ_２であり、結合ａが存在しない場合、ＯＨであり、
ｒは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ²¹ and R ²³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ²² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ²⁴ and R ²⁵ are the same or different and are each a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ² is CH or N,
Z ² is oxygen or sulfur;
^W2 is oxygen or _CH2 when bond a is present, and OH when bond a is absent;
r is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

Regarding formula (G), R ¹ , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , a substituent of a 5-membered heterocyclic group in the case of A, or 2 to 6 substituents in the case of B Examples of alkyl groups having 1 to 8 carbon atoms which can be substituents in alkylene chains having carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl and Contains hexyl.

R ¹ , R ⁴ , 2 to 8 groups which can be substituents of a 5-membered heterocyclic group in the case of A or substituents of an alkylene chain having 2 to 6 carbon atoms in the case of B Examples of alkenyl groups having carbon atoms include vinyl and allyl.

R ¹ , R ⁴ , 2 to 8 groups which can be substituents of a 5-membered heterocyclic group in the case of A or substituents of an alkylene chain having 2 to 6 carbon atoms in the case of B Examples of alkynyl groups having carbon atoms include propargyl.

Examples of 3- to 7-membered cycloalkyl groups can be substituents of 5-membered heterocyclic groups in case of A or substituents of alkylene chains having 2 to 6 carbon atoms in case of B. includes cyclopropyl, cyclopentyl and cyclohexyl.

R ¹ , R ⁴ , 1 to 8 groups which can be substituents of a 5-membered heterocyclic group in the case of A or substituents of an alkylene chain having 2 to 6 carbon atoms in the case of B Examples of alkoxy groups having carbon atoms include methoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy and hexyloxy.

Examples of halogen atoms that can be substituted for R ¹ , R ⁴ or the alkylene chain having 2 to 6 carbon atoms in the case of B include fluorine, chlorine and bromine.

R ¹ , R ⁴ , R ⁵ , R ⁶ can be a substituent of a 5-membered heterocyclic group in the case of A, or a substituent of an alkylene chain having 2 to 6 carbon atoms in the case of B Examples of possible alkyl groups having 1 to 8 carbon atoms and halogen atom substituents include methyl, ethyl, propyl, isopropyl, butyl and Contains t-butyl. In some embodiments, the alkyl group having 1-8 carbon atoms and halogen atom substituents is trifluoromethyl, chloromethyl, chloroethyl, 2-bromoethyl or 2-fluoroethyl.

R ¹ , R ⁴ , 1 to 8 groups which can be substituents of a 5-membered heterocyclic group in the case of A or substituents of an alkylene chain having 2 to 6 carbon atoms in the case of B Examples of alkoxy groups having carbon and halogen atom substituents include methoxy, ethoxy, propoxy, isopropyloxy, butyloxy and t-butyloxy, with substituents such as 1 to 3 fluorine, chlorine or bromine atoms. It will be done. In some embodiments, an alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent is trifluoromethyloxy, chloroethyloxy, 2-chloroethyloxy, 2-bromoethyloxy or 2-fluoroethyl It's oxy.

Examples of acyl groups having 2 to 8 carbon atoms that can be R ¹ or R ⁴ include acetyl and propionyl.

Examples of aryl groups having 6 to 10 carbon atoms that can be substituted for R ¹ , R ⁴ or the 5-membered heterocyclic group in the case of A include phenyl.

Examples of 5- or 6-membered heterocyclic groups that can be substituents for R ¹ , R ⁴ , or the 5-membered heterocyclic group in the case of A include pyridyl.

Examples of alkyl groups having 1 to 8 carbon atoms and 3 to 7 cycloalkyl group substituents that can be substituents of the 5-membered heterocyclic group in case A include cyclopropyl, cyclopentyl or with a cyclohexyl substituent, methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl and hexyl.

Examples of aralkyl groups (having an aryl part of 6 to 10 carbon atoms and an alkylene part of 1 to 8 carbon atoms) that can be substituents of the 5-membered heterocyclic group in case A include , benzyl and phenethyl.

Examples of alkyl groups having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic group that can be substituents of the 5-membered heterocyclic group in A include the pyridyl substituent methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl and hexyl.

Alkyl group having 1 to 8 carbon atoms, alkenyl having 2 to 8 carbon atoms, which can be R ¹¹ or R ¹³ of formula (H) or R ²¹ or R ²³ of formula (J) groups, alkynyl groups with 2 to 8 carbon atoms, alkoxy groups with 1 to 8 carbon atoms, halogen atoms, alkyl groups with 1 to 8 carbon atoms and halogen atom substituents, 1 to 8 Examples of alkoxy groups with carbon atoms and halogen atom substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms, and 5- or 6-membered heterocyclic groups are as described herein above for R ¹ and R ⁴ of formula (G).

R ¹² of formula (H) or R ²² of formula (J), an alkyl group having 1 to 8 carbon atoms, a 3 to 7 membered cycloalkyl group, 2 to 8 carbon atoms alkenyl group having 2 to 8 carbon atoms, alkynyl group having 2 to 8 carbon atoms, alkoxy group having 1 to 8 carbon atoms, alkyl group having 1 to 8 carbon atoms and a 3 to 7 membered cycloalkyl group substituent group, an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent, an alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent, an aryl group having 6 to 10 carbon atoms, 5-membered or a 6-membered heterocyclic group, an aralkyl group having an aryl portion of 6 to 10 carbon atoms and an alkylene portion of 1 to 8 carbon atoms, and an aralkyl group having an aryl portion of 1 to 8 carbon atoms and a 5- or 6-membered Examples of alkyl groups having heterocyclic substituents include those described herein above with respect to the substituents of the 5-membered heterocyclic group for A of formula (G).

Alkyl groups having 1 to 8 carbon atoms, which can be R ¹⁴ or R ¹⁵ of formula (H) or R ²⁴ or R ²⁵ of formula (J), and 1 to 8 carbon atoms and halogens Examples of alkyl groups with atomic substituents include those described herein above with respect to R ⁵ and R ⁶ of formula (G).

R ¹ in formula (G), R ¹¹ in formula (H), and R ²¹ in formula (J) may be bonded to a benzene ring or the like in singular or plural numbers (1 to 3). When each of R ¹ , R ¹¹ and R ²¹ is present in plurality, the plurality of groups can be the same or different.

R ⁴ in formula (G), R ¹³ in formula (H), and R ²³ in formula (J) may be bonded to a benzene ring or the like in singular or plural numbers (1 to 3). When each of R ⁴ , R ¹³ and R ²³ is present in plurality, the plurality of groups can be the same or different.

The substituent group of the 5-membered heterocyclic group in the case of A in formula (G), R ¹² in formula (H), and R ²² in formula (J) are singular or plural (1 or 2 ) to the heterocyclic ring. When each of the substituent groups R ¹² and R ²² of the 5-membered heterocyclic group in A is present, the plurality of groups can be the same or different.

The compounds of formulas (G), (H) and (J) can be pharmacologically acceptable salts such as alkali metal salts, for example sodium, potassium or lithium salts.

The compounds of formulas (G), (H) and (J) exist in optically active forms and in the form of optical isomers, such as racemic compounds, or in geometric isomers, such as cis or trans compounds. can do.

In some embodiments, the compound of formula (G), (H) or (J) is a compound shown in Table 5, or a pharmaceutically acceptable salt, solvate, ester, amide or It is a prodrug.

5.2.8. Compounds of Formula (K) In some embodiments, compounds of the invention are compounds of Formula (K):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ａは、ＣＨまたは窒素であり、
Ｂは、結合ａが存在する場合、酸素またはＣ（Ｒ^８）（Ｒ^９）であり、Ｒ^８およびＲ^９はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、結合ａが存在しない場合、Ｂは、ＯＨであり、
Ｗ^１は、結合、Ｃ（＝Ｏ）または（Ｃ（Ｒ^１０）（Ｒ^１１））_ｍであり、Ｒ^１０およびＲ^１１はそれぞれ、独立して、水素またはＣ_１～８アルキル基であり、ｍは、１、２または３であり、
ＸおよびＹは、互いに異なっており、各々は、酸素原子、硫黄原子、窒素原子またはＣＲ^１２であり、Ｒ^１２は、水素またはＣ_１～８アルキルであり、
Ｚ^１は、結合、酸素、硫黄またはＣ（Ｒ^１３）（Ｒ^１４）であり、Ｒ^１３およびＲ^１４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｒ^１、Ｒ^２およびＲ^３はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^４およびＲ^５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
Ｒ^６およびＲ^７はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニルまたはＣ_１～８ハロアルキルであり、
ｒは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is CH or nitrogen,
B is oxygen or C(R ⁸ )(R ⁹ ) when bond a is present, R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and when bond a is present If not, B is OH;
W ¹ is a bond, C(=O) or (C(R ¹⁰ )(R ¹¹ )) _m , R ¹⁰ and R ¹¹ are each independently hydrogen or a C _1-8 alkyl group, m is 1, 2 or 3;
X and Y are different from each other, each is an oxygen atom, a sulfur atom, a nitrogen atom or CR ¹² , and R ¹² is hydrogen or C _1-8 alkyl;
Z ¹ is a bond, oxygen, sulfur or C(R ¹³ )(R ¹⁴ ), R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
R ¹ , R ² and R ³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl or C _1-8 haloalkyl;
r is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In formula (K), in the case of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² , R ¹³ and R ¹⁴ Examples of alkyl groups having 1 to 8 carbon atoms include methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl and hexyl.

Examples of alkenyl groups having 2 to 8 carbon atoms for R ¹ , R ² , R ³ , R ⁶ and R ⁷ include vinyl and allyl.

Examples of alkynyl groups having 2 to 8 carbon atoms for R ¹ , R ² , R ³ , R ⁶ and R ⁷ include propargyl.

Examples of alkoxy groups having 1 to 8 carbon atoms for R ¹ , R ² and R ³ include methoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy and hexyl. Contains oxy.

Examples of halogen atoms for R ¹ , R ² and R ³ include fluorine, chlorine and bromine.

Examples of alkyl groups having 1 to 8 carbon atoms substituted by halogen atoms in the case of R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ include fluorine, chlorine and Includes methyl, ethyl, propyl, isopropyl, butyl and t-butyl substituted with 1 to 3 halogen atoms such as bromine. In one embodiment, the substituent is trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl or 2-fluoroethyl.

Examples of alkoxy groups having 1 to 8 carbon atoms substituted by halogen atoms in the case of R ¹ , R ² and R ³ include those substituted by 1 to 3 halogen atoms such as fluorine, chlorine or bromine; Includes methoxy, ethoxy, propoxy, isopropoxy, butoxy and t-butoxy. In one embodiment, the substituent is trifluoromethyloxy, chloroethyloxy, 2-chloroethyloxy, 2-bromoethyloxy or 2-fluoroethyloxy.

Examples of acyl groups having 2 to 8 carbon atoms for R ¹ , R ² and R ³ include acetyl and propionyl.

Examples of aryl groups having 6 to 10 carbon atoms for R ¹ , R ² and R ³ include phenyl.

Examples of 5- or 6-membered heterocyclic groups for R ¹ , R ² and R ³ include pyridyl.

R ¹ , R ² and R ³ in formula (K) can be bonded to a benzene ring, etc. in numbers of 1 to 3, and in this case, the same group or different groups can be bonded to the same ring. .

The compounds provided herein, represented by formula (K), can be in the form of pharmacologically acceptable salts such as alkali metal salts, such as sodium, potassium and lithium salts.

The compounds provided herein can exist in optically active forms and in the form of optical isomers, such as racemic compounds, or geometric isomers, such as cis or trans compounds.

In some embodiments, the compound of formula (K) is a compound shown in Table 6, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.9. Compounds of Formula (L) In some embodiments, compounds of the invention are compounds of Formula (L):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｂは、結合ａが存在する場合、酸素であり、結合ａが存在しない場合、Ｂは、ＯＨであり、
Ｗ^２は、結合、Ｃ（＝Ｏ）またはＣＨ_２であり、
Ｚ^２は、酸素または硫黄であり、
Ｒ^２１、Ｒ^２２およびＲ^２３はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２４およびＲ^２５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B is oxygen when bond a is present; B is OH when bond a is absent;
^W2 is a bond, C(=O) or _CH2 ,
Z ² is oxygen or sulfur;
R ²¹ , R ²² and R ²³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ²⁴ and R ²⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In formula (L), in the case of R ²¹ , R ²² and R ²³ an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms; Alkynyl group, alkoxy group having 1 to 8 carbon atoms, halogen atom, alkyl group having 1 to 8 carbon atoms substituted by halogen atom, 1 to 8 carbon atoms substituted by halogen atom Alkoxy groups with atoms, hydroxyl, nitro, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms, and 5- or 6-membered heterocyclic groups include some In embodiments, R ¹ , R ² and R ³ in formula (K) may be as described above.

In formula (L), the alkyl group having 1 to 8 carbon atoms and the alkyl group having 1 to 8 carbon atoms substituted by a halogen atom in the case of R ²⁴ and R ²⁵ are In embodiments, the cases of R ⁴ and R ⁵ in formula (K) may be as described.

R ²¹ , R ²² and R ²³ in formula (L) can be bonded to a benzene ring or the like in numbers of 1 to 3, and in this case, the same group or different groups can be bonded to the same ring. .

The compounds provided herein, represented by formula (L), can be in the form of pharmacologically acceptable salts such as alkali metal salts, such as sodium, potassium and lithium salts.

The compounds provided herein can exist in optically active forms and in the form of optical isomers, such as racemic compounds, or geometric isomers, such as cis or trans compounds.

5.2.10. Compounds of Formula (M) and (N) In some embodiments, compounds of the invention include compounds of Formula (M):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、窒素またはＣＨであり、
Ｘは、窒素またはＣＨであり、
Ｙは、酸素または硫黄であり、
Ｚは、結合、酸素、硫黄またはＮＲ^５であり、Ｒ^５は、水素またはＣ_１～８アルキルであり、
Ｒ^１およびＲ^２はそれぞれ、独立して、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員または６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレンを有するアラルキル基または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキルであり、
Ｒ^３およびＲ^４はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ａは、ピラゾール、チオフェン、フラン、イソオキサゾール、イソチアゾールまたはピロールである５員の複素環であり、５員の複素環は、無置換であるか、あるいはハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基により置換されており、
Ｂは、結合またはＣ_１～８アルキレンであり、Ｃ_１～８アルキレンは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_１～８アルコキシもしくはハロゲン置換基により置換されており、場合により、Ｃ_１～８アルキレンは二重結合または三重結合を有しており、
ｒは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently nitrogen or CH;
X is nitrogen or CH,
Y is oxygen or sulfur;
Z is a bond, oxygen, sulfur or NR ⁵ and R ⁵ is hydrogen or C _1-8 alkyl;
R ¹ and R ² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl with 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R ³ and R ⁴ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
A is a 5-membered heterocycle which is pyrazole, thiophene, furan, isoxazole, isothiazole or pyrrole, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _{1 ~8} alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl with 3-7 membered cycloalkyl substituent, C _{1 ~8} haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a 5- or substituted with a C _1-8 alkyl group having a 6-membered heterocyclic substituent,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _1-8 alkoxy or halogen substituent optionally, the C _1-8 alkylene has a double or triple bond,
r is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (N):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｗ^３は、窒素またはＣＨであり、
Ｚ^１は、酸素または硫黄であり、
Ｒ^１１およびＲ^１２はそれぞれ、独立して、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルキルまたはＣ_１～８ハロアルコキシであり、
Ｒ^１３およびＲ^１４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ａ^１は、ピラゾールまたはチオフェンである５員の複素環であり、５員の複素環は、無置換であるか、またはハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルキルもしくはＣ_１～８ハロアルコキシにより置換されており、
ｍは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^W3 is nitrogen or CH,
Z ¹ is oxygen or sulfur;
R ¹¹ and R ¹² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl, or C _1-8 haloalkoxy;
R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
A ¹ is a 5-membered heterocycle that is pyrazole or thiophene, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 alkoxy , substituted by C _1-8 haloalkyl or C _1-8 haloalkoxy,
m is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments of the compounds of formula (M), an alkyl group having 1 to 8 carbon atoms in R ¹ , R ² , R ³ , R ⁴ , R ⁵ , a 5-membered heterocycle in A; and substituents attached to alkylene chains having 1 to 8 carbon atoms, if any, are methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t- It can be butyl, pentyl or hexyl.

In one embodiment, the alkenyl group having 2 to 8 carbon atoms for R ¹ , R ² and the substituents are attached to the 5-membered heterocycle of A and are vinyl or allyl.

In one embodiment, the alkynyl group having 2 to 8 carbon atoms for R ¹ , R ² in which the substituent is attached to the 5-membered heterocycle of A is propargyl. .

In one embodiment, a 3- to 7-membered cycloalkyl group for R ¹ , R ² where the substituent is attached to the 5-membered heterocycle of A. In another embodiment, the substituent is attached to an alkylene chain having 1 to 8 carbon atoms and is cyclopentyl or cyclohexyl.

In one embodiment, an alkoxy group having 1 to 8 carbon atoms in the case of R ¹ , R ² where the substituent is attached to the 5-membered heterocycle of A. In another embodiment, the substituent is attached to an alkylene chain having 1 to 8 carbon atoms and includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, i-butoxy, t-butoxy, pentyloxy or hexyl It's oxy.

In one embodiment, R ¹ and R ² are halogen and the substituents are attached to A's 5-membered heterocycle. In another embodiment, the substituent is attached to an alkylene chain having 1 to 8 carbon atoms and is fluorine, chlorine or bromine.

In one embodiment, an alkyl group having 1 to 8 carbon atoms and a halogen substituent for R1, R2, R5, wherein the substituent is attached to the 5-membered heterocycle of A. is methyl, ethyl, propyl, isopropyl, butyl or t-butyl with 1 to 3 halogen substituents such as fluorine, chlorine or bromine. In another embodiment, the substituents are selected from trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl and 2-fluoroethyl.

In one embodiment, an alkoxy group having 1 to 8 carbon atoms and a halogen substituent in R ¹ , R ² , wherein the substituent is attached to the 5-membered heterocycle of A. is methoxy, ethoxy, propoxy, isopropoxy, butyloxy or t-butyloxy with 1 to 3 halogen substituents such as fluorine, chlorine or bromine. In one embodiment, the substituents are selected from trifluoromethyloxy, chloroethyloxy, 2-chloroethyloxy, 2-bromoethyloxy and 2-fluoroethyloxy.

In one embodiment, R ¹ , an aryl group having 6 to 10 carbon atoms in R ² , and a substituent attached to the 5-membered heterocycle of A is phenyl.

In one embodiment, R ¹ , the 5- or 6-membered heterocyclic group of R ² , and the substituent are attached to the 5-membered heterocycle of A and are pyridyl.

In one embodiment, an alkyl group having 1 to 8 carbon atoms and a 3 to 7 membered cycloalkyl group in the case of R ¹ , R ² and the substituent is attached to the 5-membered heterocycle of A. methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl or hexyl, with a cyclopropyl, cyclopentyl or cyclohexyl substituent.

In one embodiment, R ¹ , aralkyl having an aryl moiety of 6 to 10 carbon atoms and an alkylene moiety of 1 to 8 carbon atoms when R ² and the substituents are the 5-membered heterocycle of A is attached to benzyl or phenethyl.

In one embodiment, R ¹ , an alkyl group having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic group in R ² and the substituents are attached to the 5-membered heterocycle of A. methyl, ethyl, propyl, isopropyl, butyl, i-butyl, t-butyl, pentyl or hexyl with a pyridyl substituent.

In one embodiment, the optionally substituted 5-membered heterocycle in A is a pyrazole or thiophene having a substituent. In another embodiment, the pyrazole has a substituent.

In one embodiment, the substituted alkylene chain of 1 to 8 carbon atoms in case B is an alkylene chain of 1 to 4 carbon atoms. In another embodiment, the alkylene chain is an ethylene chain or a propylene chain.

In one embodiment, n is 0.

In certain embodiments of the compounds of formula (N), halogen atoms in R ¹¹ and R ¹² , alkyl groups having 1 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, 1 to 8 Alkyl groups having 1 to 8 carbon atoms and halogen substituents, and alkoxy groups having 1 to 8 carbon atoms and halogen substituents are those described earlier in the specification with respect to R ¹ and R ² of formula (M). It can be assumed that

In one embodiment, the alkyl group having 1 to 8 carbon atoms in the case of R ¹³ and R ¹⁴ is as described earlier herein with respect to R ³ and R ⁴ of formula (M). can do.

In one embodiment, when A ¹ in formula (N), a halogen atom, an alkyl group having 1 to 8 carbon atoms, having 1 to 8 carbon atoms, is attached to the pyrazole or thiophene. The alkoxy group, the alkyl group having 1 to 8 carbon atoms and a halogen substituent, and the alkoxy group having 1 to 8 carbon atoms and a halogen substituent include the 5-membered heterocycle of A in formula (M). The attached substituents are as described earlier in the specification.

In one embodiment, R ¹ of formula (M) and R ¹¹ of formula (N), such as a benzene ring, can have from 1 to 3 numbers of R ¹ or R ¹¹ , which are the same or , or different from each other. In another embodiment, a benzene ring, etc. can have 1 to 3 substituents other than hydrogen atoms.

In one embodiment, R ² of formula (M) and R ¹² of formula (N), such as the benzene ring of the benzisoxazole ring, can have a number of R ² or R ¹² from 1 to 3, and these are , the same or different from each other. In another embodiment, a benzene ring, such as a benzisoxazole ring, can have 1 to 3 substituents other than hydrogen atoms.

In one embodiment, the substituent attached to the 5-membered heterocycle in case of A of formula (M) and the substituent attached to the pyrazole or thiophene in case of A ¹ of formula (N) is There can be one or two numbers, which can be the same or different from each other.

The compounds provided herein, represented by formulas (M) and (N), are in the form of pharmacologically acceptable salts such as alkali metal salts, for example sodium, potassium and lithium salts. obtain.

The compounds provided herein can exist in optically active forms and in the form of optical isomers, such as racemic compounds, or geometric isomers, such as cis or trans compounds.

In some embodiments, the compound of formula (M) or (N) is a compound shown in Table 7, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. .

5.2.11. Compounds of Formula (O), (P) and (Q) In some embodiments, compounds of the invention include compounds of Formula (O):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、ＣＨまたは窒素であり、
Ｘは、ＮＲ^５またはＣＲ^６Ｒ^７であり、Ｒ^５は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシにより置換されているＣ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_３～７シクロアルキルにより置換されているＣ_１～８アルキル、フェニルにより置換されているＣ１～８アルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、Ｒ^６およびＲ^７はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｙは、（ＣＲ^８Ｒ^９）_ｒであり、Ｒ^８およびＲ^９はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、ｒは、１、２、３または４であるか、あるいは
ＸおよびＹは、一緒になって、ＣＲ^１０＝ＣＲ^１１またはエチニレンを形成し、Ｒ^１０およびＲ^１１はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｇは、結合ａが存在する場合、Ｏ、ＳまたはＣＲ^１２Ｒ^１３であり、Ｒ^１２およびＲ^１３はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、結合ａが存在しない場合、Ｇは、ＯＨであり、
Ａは、チアゾール、オキサゾール、イミダゾール、ピラゾール、チオフェン、フランまたはピロールである５員の複素環式環であり、複素環式環は、無置換であるか、あるいはＣ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基により置換されており、
Ｂは、Ｃ_１～８アルキレン鎖、Ｃ_２～８アルケニレン鎖またはＣ_２～８アルキニレン鎖であり、これらの鎖は、無置換であるか、またはＣ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_１～８アルコキシもしくはハロゲンにより置換されており、
Ｒ^１およびＲ^２はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^３およびＲ^４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
ｍは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or nitrogen;
X is NR ⁵ or CR ⁶ R ⁷ and R ⁵ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, C _{3-8 7} cycloalkyl, C _1-8 alkyl substituted by C _3-7 cycloalkyl, C 1-8 alkyl substituted by phenyl, C _2-8 acyl or C _2-8 alkenyl, R ⁶ and R each ⁷ is independently hydrogen or C _1-8 alkyl;
Y is (CR ⁸ R ⁹ ) _r , R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4, or X and Y are taken together to form CR ¹⁰ =CR ¹¹ or ethynylene, and R ¹⁰ and R ¹¹ are each independently hydrogen or C _1-8 alkyl;
G is O, S or CR ¹² R ¹³ when bond a is present, R ¹² and R ¹³ are each independently hydrogen or C _1-8 alkyl, and when bond a is absent, G is OH,
A is a 5-membered heterocyclic ring which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan or pyrrole, and the heterocyclic ring is unsubstituted or C _1-8 alkyl, C _{2-8 8} alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _{1-8 haloalkyl, C 1-8} haloalkoxy, _hydroxyl , nitro, C _2-8 acyl, C _6-10 aryl or 5-membered or 6-membered substituted with a member heterocyclic group,
B is a C _1-8 alkylene chain, a C _2-8 alkenylene chain, or a C _2-8 alkynylene chain, and these chains are unsubstituted or C _1-8 alkyl, C _3-7 cycloalkyl , substituted by C _1-8 alkoxy or halogen,
R ¹ and R ² are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
R ³ and R ⁴ are each independently hydrogen or C _1-8 alkyl;
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (P):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｇ^ａは、結合ａが存在する場合、Ｏ、ＳまたはＣＨ_２であり、結合ａが存在しない場合、Ｇ^ａは、ＯＨであり、
Ａ^ａは、チアゾール、オキサゾールまたはチオフェンである５員の複素環式環であり、５員の複素環式環は、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロもしくはＣ_２～８アシルにより置換されており、
Ｂ^ａは、Ｃ_１～８アルキレン鎖またはＣ_２～８アルケニレン鎖であり、
Ｒ^１ａおよびＲ^２ａはそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロまたはＣ_２～８アシルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^a is O, S or CH ₂ when bond a is present; when bond a is absent, G ^a is OH;
A ^a is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, halogen , C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^a is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1a and R ^2a are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (Q):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｇ^ｂは、結合ａが存在する場合、Ｏ、ＳまたはＣＨ_２であり、結合ａが存在しない場合、Ｇ^ｂは、ＯＨであり、
Ａ^ｂは、チアゾール、オキサゾールまたはチオフェンである５員の複素環式環であり、５員の複素環式環は、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロもしくはＣ_２～８アシルにより置換されており、
Ｂ^ｂは、Ｃ_１～８アルキレン鎖またはＣ_２～８アルケニレン鎖であり、
Ｒ^１ｂおよびＲ^２ｂはそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロまたはＣ_２～８アシルであり、
Ｒ^３ｂは、水素またはＣ_１～８アルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^b is O, S or CH ₂ when bond a is present, and G ^b is OH when bond a is absent;
A ^b is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, halogen , C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^b is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1b and R ^2b are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^3b is hydrogen or C _1-8 alkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, in formula (O), R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R 7 , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ , ^{R 12 ,} R ¹³ , the substituent of the 5-membered heterocyclic ring represented by A, and the substituent of the C _1-8 alkylene chain, C _2-8 alkenylene chain or C _2-8 alkynylene chain represented by B are C It can be _1-8 alkyl. Examples of C _1-8 alkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , R ⁵ , and A can be C _2-8 alkenyl. Examples of C _2-8 alkenyl include vinyl and allyl.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , and A can be C _2-8 alkynyl. Examples of C _2-8 alkynyl include propargyl.

In one embodiment, R ¹ , R ² , a substituent of the 5-membered heterocyclic ring represented by A, and a C _1-8 alkylene chain, a C _{2-8 alkenylene chain, or a C 2-8 alkenylene} chain represented by B The substituents on the _8- alkynylene chain can be C _1-8 alkoxy. Examples of C _1-8 alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy and hexyloxy.

In one embodiment, R ¹ , R ² , a substituent of the 5-membered heterocyclic ring represented by A, and a C _1-8 alkylene chain, a C _{2-8 alkenylene chain, or a C 2-8 alkenylene} chain represented by B The substituents on the _8- alkynylene chain can be halogens. Examples of halogens include fluorine, chlorine and bromine.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , R ⁵ , and A can be C _1-8 alkyl substituted with halogen. Examples of C _1-8 alkyl substituted by halogen include methyl, ethyl, propyl, isopropyl, butyl and t-butyl substituted by 1 to 3 halogens such as fluorine, chlorine and bromine. It will be done. Trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl and 2-fluoroethyl are preferred.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , and A can be C _1-8 alkoxy substituted with halogen.

Examples of C _1-8 alkoxy substituted by halogen include methoxy, ethoxy, propoxy, isopropoxy, butoxy and Contains a t-butoxy group. In one embodiment, R ¹ , R ² , and the substituents on the 5-membered heterocyclic ring are trifluoromethoxy, chloromethoxy, 2-chloroethoxy, 2-bromoethoxy, and 2-fluoroethoxy.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , R ⁵ , and A can be C _2-8 acyl. Examples of C _2-8 acyl include acetyl and propionyl.

In one embodiment, the substituents on the 5-membered heterocyclic ring represented by R ¹ , R ² , and A are C^. It can be a ¥Q aryl. Examples of C _6-10 aryl include phenyl.

In one embodiment, the substituents of the 5-membered heterocyclic ring represented by R ¹ , R ² , and A can be 5- or 6-membered heterocyclic groups. Examples of 5- or 6-membered heterocyclic groups include pyridyl.

In one embodiment, R ⁵ can be C _1-8 alkyl substituted with C _1-8 alkoxy.

Examples of C _1-8 alkyl substituted by C _1-8 alkoxy include methyl, substituted by methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy or hexyloxy; Includes ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl.

In one embodiment, R ⁵ can be a 3- to 7-membered cycloalkyl. Examples of 3- to 7-membered cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In one embodiment, R ⁵ can be C _1-8 alkyl substituted with a 3- to 7-membered cycloalkyl. Examples of C _1-8 alkyl substituted by 3- to 7-membered cycloalkyl include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, substituted by cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; Includes t-butyl, pentyl and hexyl.

In one embodiment, R ⁵ can be C _1-8 alkyl substituted with phenyl.

Examples of C _1-8 alkyl substituted with phenyl include benzyl and phenethyl.

In one embodiment, the substituent of the C _1-8 alkylene chain, C _2-8 alkenylene chain or C _2-8 alkynylene chain represented by B can be a 3- to 7-membered cycloalkyl. Examples of 3- to 7-membered cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

In some embodiments, the substituents of the 5-membered heterocyclic ring represented by R ^1a , R ^2a , and A ^a in formula (P) are C _1-8 alkyl, C _1-8 alkoxy, It can be halogen, C _1-8 alkyl substituted by halogen, C _1-8 alkoxy and C _2-8 acyl substituted by halogen. Examples thereof are the same as those of the substituents of the 5-membered heterocyclic ring represented by R ¹ , R ² and A in formula (O).

In some embodiments, in formula (Q), the substituents on the 5-membered heterocyclic ring represented by R ^1b , R ^2b , and A ^b are C _1-8 alkyl, C _1-8 alkoxy, It can be halogen, C _1-8 alkyl substituted by halogen, C _1-8 alkoxy and C _2-8 acyl substituted by halogen. Examples thereof are the same as those of the substituents of the 5-membered heterocyclic ring represented by R ¹ , R ² and A in formula (O).

In one embodiment, in formula (Q), R ^3b can be C _1-8 alkyl. Examples are the same as those for R ⁵ in formula (O).

In one embodiment, R ¹ , R 2 in formula (O), R ^1a , R ^{2a in formula (P), and R 1b and R 2b} in formula (Q) each represent a ring, such as a benzene ring. There can be from 1 to 3 groups attached. The two or three groups may be different from each other.

Compounds having formulas (O), (P) and (Q) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

Compounds of formula (O), (P) and (Q) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

In some embodiments, the compound of formula (O), (P) or (Q) is a compound shown in Table 8, or a pharmaceutically acceptable salt, solvate, ester, amide or It is a prodrug.

5.2.12. Compounds of Formula (R) and (S) In some embodiments, compounds of the invention include compounds of Formula (R):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、ＣＨまたはＮであり、
Ｘは、ＮＲ^３またはＣＲ^４Ｒ^５であり、Ｒ^３は、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシにより置換されているＣ_１～８アルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、フェニル基により置換されているＣ_１～８アルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｙは、（ＣＲ^６Ｒ^７）_ｒであり、Ｒ^６およびＲ^７はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、ｒは、１、２、３または４であり、
Ａは、チアゾール、オキサゾール、イミダゾール、ピラゾール、チオフェン、フラン、ピロール、ピリジンまたはピリミジンである５員もしくは６員の複素環式基あるいはフェニル基であり、５員もしくは６員の複素環式基またはフェニル基は、無置換であるか、あるいはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシル、３～７員のシクロアルキル基により置換されているＣ_１～８アルキル基、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５もしくは６員の複素環式基、Ｃ_６～１０アリール基およびＣ_１～８アルキル基を含むアラルキル基、または５員もしくは６員の複素環式基により置換されているＣ_１～８アルキル基により置換されており、
Ｂは、結合またはＣ_１～８アルキレンであり、Ｃ_１～８アルキレンは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_１～８アルコキシもしくはハロゲンにより置換されており、かつアルキレン鎖の炭素数が２個以上である場合、二重結合または三重結合を有してもよく、
Ｄは、ＮまたはＣＨであり、
Ｅは、ＯまたはＳであり、
Ｒ^１およびＲ^２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
ｍは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or N,
X is NR ³ or CR ⁴ R ⁵ and R ³ is C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, 3-7 membered C _1-8 alkyl substituted by cycloalkyl, C _1-8 alkyl substituted by phenyl group, C _2-8 acyl or C _2-8 alkenyl,
R ⁴ and R ⁵ are each independently hydrogen or C _1-8 alkyl;
Y is (CR ⁶ R ⁷ ) _r , R ⁶ and R ⁷ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4;
A is a 5- or 6-membered heterocyclic group that is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, pyrrole, pyridine or pyrimidine, or a phenyl group; A is a 5- or 6-membered heterocyclic group or phenyl; The group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxyl, 3-7 membered cycloalkyl group. C _{1-8 alkyl group, C 1-8 haloalkyl} , C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _{6-10 aryl group and C 1-8 aryl} group substituted with substituted by an aralkyl group containing _~8 alkyl group, or a C _1-8 alkyl group substituted by a 5- or 6-membered heterocyclic group,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or substituted by C _1-8 alkyl, 3-7 membered cycloalkyl group, C _1-8 alkoxy or halogen. If it is substituted and the number of carbon atoms in the alkylene chain is 2 or more, it may have a double bond or triple bond,
D is N or CH;
E is O or S;
R ¹ and R ² are each independently H, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, the compounds of the invention are of formula (S):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ａ^１は、チアゾール、オキサゾール、ピリジンもしくはピリミジンである５員または６員の複素環式基、あるいはフェニル基であり、５もしくは６員の複素環式基またはフェニル基は、無置換であるか、またはＣ_１～８アルキルまたはＣ_１～８ハロアルキルにより置換されており、
Ｂ^１は、Ｃ_２～４アルキレンであり、
Ｒ^１１およびＲ^１２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、ハロゲンまたはＣ_１～８ハロアルキルであり、
Ｒ^１３は、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、場合によりＲ^１３が結合しているＮは、ベンゾイソオキサゾールの第６位に結合しており、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A ¹ is a 5- or 6-membered heterocyclic group such as thiazole, oxazole, pyridine or pyrimidine, or a phenyl group, and the 5- or 6-membered heterocyclic group or phenyl group is unsubstituted or or substituted with C _1-8 alkyl or C _1-8 haloalkyl,
B ¹ is C _2-4 alkylene;
R ¹¹ and R ¹² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ¹³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ¹³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments of compounds having formula (R), both W ¹ and W ² are CH.

In some embodiments of compounds having formula (R), X is CR ⁴ R ⁵ , CH ₂ or NR 3 ^{and R 3 is} an alkyl group having 1-8 carbon atoms. In another embodiment, R ³ is a methyl group.

In some embodiments of compounds having formula (R), Y is _CH2 .

In some embodiments of compounds having formula (R), Z is a carboxyl group.

In some embodiments of compounds having formula (R), A is an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, or an alkenyl group having 2 to 8 carbon atoms. selected from the group consisting of an alkynyl group having 1 to 8 carbon atoms and a halogen atom substituent, an aryl group having 6 to 10 carbon atoms or a 5- or 6-membered heterocyclic group Thiazole or oxazole, which may have a substituent; alkyl group having 1 to 8 carbon atoms, alkenyl group having 2 to 8 carbon atoms, alkynyl group having 2 to 8 carbon atoms, 1 having a substituent selected from the group consisting of an alkyl group having ~8 carbon atoms and a halogen atom substituent, an aryl group having 6 to 10 carbon atoms, or a 5- or 6-membered heterocyclic group. It is a good pyrazole.

In some embodiments of compounds having formula (R), B is an ethylene chain.

In some embodiments of compounds having formula (R), D is N.

In some embodiments of compounds having formula (R), E is O.

In some embodiments of compounds having formula (R), R ¹ and R ² are each independently H, an alkyl group having 1 to 8 carbon atoms, and having 2 to 8 carbon atoms. Alkenyl group, alkoxy group having 1 to 8 carbon atoms, halogen atom, alkyl group having 1 to 8 carbon atoms and a halogen atom substituent, or alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent It is the basis.

In some embodiments of compounds having formula (R), m is 0.

In some embodiments of compounds having formula (S), R ¹³ is an alkyl group having 1-8 carbon atoms. In another embodiment, R ¹³ is a methyl group.

In some embodiments of compounds having formula (S), p is 1.

In some embodiments of compounds having formula (S), A ¹ is an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent. thiazole, oxazole or phenyl, which may have a substituent selected from thiazole, oxazole or phenyl. In another embodiment, A ¹ is thiazole which may have an alkyl group having 1 to 8 carbon atoms as a substituent.

In some embodiments of compounds having formula (S), B ¹ is an ethylene chain.

In some embodiments of compounds having formula (S), R ¹¹ is an alkyl group having 1 to 8 carbon atoms, a halogen atom, or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent. It is.

In some embodiments of compounds having formula (S), R ¹² is H, an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent. be.

Compounds of formula (R) and (S) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

Compounds having formulas (R) and (S) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

In some embodiments, the compound of formula (R) or (S) is a compound shown in Table 9, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. .

5.2.13. Compounds of Formula (T) In some embodiments, compounds of the invention are compounds of Formula (T):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｂ^２は、Ｃ_２～４アルキレンであり、
Ｒ^２０は、Ｃ_１～８アルキルであり、
Ｒ^２１およびＲ^２２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、ハロゲンまたはＣ_１～８ハロアルキルであり、
Ｒ^２３は、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、場合によりＲ^２３が結合しているＮは、ベンゾイソオキサゾールの第６位に結合しており、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B ² is C _2-4 alkylene;
R ²⁰ is C _1-8 alkyl;
R ²¹ and R ²² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ²³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ²³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).

In some embodiments, R ²³ is an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent. In another embodiment, R ²³ is a methyl group.

In some embodiments, n is an integer from 1 to 4. In some embodiments, n is 1.

In some embodiments, R ²⁰ is an alkyl group having 1-8 carbon atoms. In another embodiment, R ²⁰ is methyl.

In some embodiments, B ² is an alkylene chain having 2-4 carbon atoms. In another embodiment, ^B2 is an ethylene chain.

In some embodiments, R ²¹ and R ²² each independently have H, an alkyl group having 1 to 8 carbon atoms, a halogen atom, 1 to 8 carbon atoms, and a halogen atom substituent. It is an alkyl group. In another embodiment, R ²¹ is an alkyl group having 1 to 8 carbon atoms, a halogen atom, or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent. In yet another embodiment, R ²² is H, an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent.

In some embodiments, N(R ²³ )((CH ₂ ) _n -R ^x ) is attached to the 6-position of the benzisoxazole.

Compounds having formula (T) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

Compounds having formula (T) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

5.2.14. Compounds of Formula (U) In some embodiments, compounds of the invention are compounds of Formula (U):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^３、Ｒ^４、Ｒ^５およびＲ^６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘは、酸素、硫黄またはＮＲ^７であり、Ｒ^７は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｙは、酸素、硫黄、ＮＲ^８または結合であり、Ｒ^８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
ｐは、０または１であり、
Ａは、結合ａが存在する場合、酸素 ＣＨ_２、Ｎ－ＮＨ_２またはＮ－ＯＲ^９であり、Ｒ^９は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシル、Ｃ_２～８アルケニルまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、結合ａが存在しない場合、Ａは、ＯＨであり、
Ｂは、ｐ＝１である場合、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、もしくはＣ_６～１０アリール部分および１～８個の炭素原子のＣ１－Ｃ８のアルキレン部分を有するアラルキル基である置換基を有するまたは有さないベンゼン環であり、ｐ＝０の場合、インドール、ベンゾフラン、ベンゾイソオキサゾールまたは１，２－ベンゾイソチアゾールである縮合環であり、前記縮合環は、置換基を有するか、または有しておらず、この置換基は、
ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ１－Ｃ８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ基、Ｃ_２～８アシル、Ｃ_６～１０アリール、またはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｙは、Ｂのベンゼン環に結合しており、
（Ｃ（Ｒ^３）（Ｒ^４））_ｍは、その３位においてＢの縮合環に結合しており、
ｍは、１～４の整数であり、
ｎは、０、１、２、３、４または５であり、
Ｙは、ｎ＝０の場合、結合であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C _1-8 alkyl, C _3-7 cycloalkyl, C2-C8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3- C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ² has hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _1-8 alkyl with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
X is oxygen, sulfur or NR ⁷ and R ⁷ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, C _{2 ~8} acyl or C _2-8 alkenyl,
Y is oxygen, sulfur, NR ⁸ or a bond, R ⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
p is 0 or 1,
A is oxygen CH ₂ , N-NH ₂ or N-OR ⁹ when bond a is present, R ⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl, an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A is OH;
When p=1, B is halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3 C 1-8 alkyl having ~7-membered cycloalkyl substituent, C _1-8 haloalkyl _{, C 1-8 alkyl} having C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, a benzene ring with or without substituents that is a C _6-10 aryl group or an aralkyl group having a C _6-10 aryl moiety and a C1-C8 alkylene moiety of 1 to 8 carbon atoms; p= If 0, it is a fused ring which is indole, benzofuran, benzisoxazole or 1,2-benziisothiazole, said fused ring has or does not have a substituent, and this substituent is
Halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl with C1-C8 alkoxy substituent, C _1-8 haloalkoxy group, C _2-8 acyl, C _6-10 aryl, or C ₆ an aralkyl group having _~10 aryl moieties and a C _1-8 alkylene moiety;
Y is bonded to the benzene ring of B,
(C(R ³ )(R ⁴ )) _m is bonded to the fused ring of B at its 3-position,
m is an integer from 1 to 4,
n is 0, 1, 2, 3, 4 or 5;
Y is a bond when n=0,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

In some embodiments, R ¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, alkyl group having 1 to 8 carbon atoms, 3 to 7 membered cycloalkyl group, 2 to 8 carbon atoms alkenyl groups having carbon atoms, alkynyl groups having 2 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, cycloalkyl substituents having 1 to 8 carbon atoms and 3 to 7 members; an alkyl group having 1 to 8 carbon atoms and a halogen substituent; an alkyl group having 1 to 8 carbon atoms and an alkoxy substituent having 1 to 8 carbon atoms; Alkoxy groups with carbon atoms and halogen substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms, 5- or 6-membered heterocyclic groups, 6 to 10 represents an aralkyl group having an aryl part of carbon atoms and an alkylene part of 1 to 8 carbon atoms, or an alkyl group having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic substituent.

In some embodiments, R ² is hydrogen, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkenyl group having 1 to 8 carbon atoms, and a 3 to 7 membered an alkyl group having a cycloalkyl substituent, an alkyl group having 1 to 8 carbon atoms and a halogen substituent, an alkyl group having an alkoxy substituent having 1 to 8 carbon atoms and 1 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, an aryl group having 6 to 10 carbon atoms, or an aralkyl group having an aryl part of 6 to 10 carbon atoms and an alkylene part of 1 to 8 carbon atoms; represents.

In some embodiments, R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, an alkyl group having 1 to 8 carbon atoms, or a halogen substituent having 1 to 8 carbon atoms. represents an alkyl group having

In some embodiments, X is oxygen, sulfur, or NR ^{7 and R 7 has} hydrogen, an alkyl group having 1 to 8 carbon atoms, 1 to 8 carbon atoms, and a halogen substituent. an alkyl group, an aralkyl group having an aryl portion of 6 to 10 carbon atoms and an alkylene portion of 1 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, or an acyl group having 2 to 8 carbon atoms; represents an alkenyl group having

In some embodiments, Y is oxygen, sulfur, NR, or a bond, and R ⁸ is hydrogen, an alkyl group having 1 to 8 carbon atoms, 1 to 8 carbon atoms, and a halogen substituent. represents an alkyl group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, or an alkenyl group having 2 to 8 carbon atoms.

In some embodiments, p is 0 or 1.

In some embodiments, A is oxygen, CH ₂ , N-NH ₂ or N-OR ⁹ and R ⁹ is hydrogen, an alkyl group having 1 to 8 carbon atoms, Alkyl groups with carbon atoms and halogen substituents, acyl groups with 2 to 8 carbon atoms, alkenyl groups with 2 to 8 carbon atoms or aryl moieties of 6 to 10 carbon atoms and 1 to 8 carbon atoms represents an aralkyl group having an alkylene moiety of carbon atoms.

In some embodiments, when p=1, B is halogen, hydroxyl, nitro, amino, alkyl group having 1 to 8 carbon atoms, 3 to 7 membered cycloalkyl group, 2 to 8 alkenyl groups having carbon atoms, alkynyl groups having 2 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, cycloalkyl substituents having 1 to 8 carbon atoms and 3 to 7 members; an alkyl group having 1 to 8 carbon atoms and a halogen substituent; an alkyl group having 1 to 8 carbon atoms and an alkoxy substituent having 1 to 8 carbon atoms; Alkoxy groups with carbon atoms and halogen substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms or aryl moieties with 6 to 10 carbon atoms and 1 to 8 carbon atoms represents a benzene ring with or without a substituent selected from the group consisting of an aralkyl group having an alkylene moiety of carbon atoms, and when p=0, indole, benzofuran, benzisoxazole and 1,2-benzoiso represents a fused ring selected from the group consisting of thiazole, the fused ring being halogen, hydroxyl, nitro, amino, alkyl group having 1 to 8 carbon atoms, 3 to 7 membered cycloalkyl group, 2 to 8 alkenyl group having 1 to 8 carbon atoms, alkynyl group having 2 to 8 carbon atoms, alkoxy group having 1 to 8 carbon atoms, cycloalkyl substituent having 1 to 8 carbon atoms and 3 to 7 members an alkyl group having 1 to 8 carbon atoms and a halogen substituent; an alkyl group having 1 to 8 carbon atoms and an alkoxy substituent having 1 to 8 carbon atoms; 1 to 8 carbon atoms; an alkoxy group having from 2 to 8 carbon atoms and a halogen substituent, an aryl group from 6 to 10 carbon atoms, or an aryl moiety from 6 to 10 carbon atoms and from 1 to with or without substituents selected from the group consisting of aralkyl groups having an alkylene moiety of 8 carbon atoms.

In some embodiments, Y is attached to the benzene ring of B.

In some embodiments, -(C(R ³ )(R ⁴ )) _m - is attached to the fused ring of B at its 3-position.

In some embodiments, m is an integer from 1 to 4.

In some embodiments, n is an integer from 0 to 5.

In some embodiments, Y is a bond when n=0.

Compounds having formula (U) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

Compounds having formula (U) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

5.2.15. Compounds of Formula (V) In some embodiments, compounds of the invention are compounds of Formula (V):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^１２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^１３、Ｒ^１４、Ｒ^１５およびＲ^１６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｙ^１は、酸素、硫黄、ＮＲ^１８または結合であり、Ｒ^１８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ａ^１は、結合ａが存在する場合、酸素 ＣＨ_２、Ｎ－ＮＨ_２またはＮ－ＯＲ^１９であり、Ｒ^１９は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシル、Ｃ_２～８アルケニルまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、結合ａが存在しない場合、Ａ^１は、ＯＨであり、
Ｑ^１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
ｒは、１、２、３または４であり、
ｓは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R11 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ¹² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ¹ is oxygen, sulfur, NR ¹⁸ or a bond, R ¹⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl,
A ¹ is oxygen CH ₂ , N-NH ₂ or N-OR ¹⁹ when bond a is present, R ¹⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl , an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A ¹ is OH;
Q ¹ is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
r is 1, 2, 3 or 4;
s is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

In some embodiments, R ¹¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, alkyl group having 1-8 carbon atoms, cycloalkyl group having 3-7 members, cycloalkyl group having 2-8 members alkenyl groups having carbon atoms, alkynyl groups having 2 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, cycloalkyl substituents having 1 to 8 carbon atoms and 3 to 7 members; alkyl groups having 1 to 8 carbon atoms and halogen substituents; alkyl groups having 1 to 8 carbon atoms and alkoxy substituents having 1 to 8 carbon atoms; Alkoxy groups with carbon atoms and halogen substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms, 5- or 6-membered heterocyclic groups, 6 to 10 represents an aralkyl group having an aryl part of carbon atoms and an alkylene part of 1 to 8 carbon atoms, or an alkyl group having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic substituent.

In some embodiments, R ¹² is hydrogen, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkenyl group having 1 to 8 carbon atoms, and a 3 to 7 membered an alkyl group having a cycloalkyl substituent, an alkyl group having 1 to 8 carbon atoms and a halogen substituent, an alkyl group having an alkoxy substituent having 1 to 8 carbon atoms and 1 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, an aryl group having 6 to 10 carbon atoms or an aralkyl group having an aryl part of 6 to 10 carbon atoms and an alkylene part of 1 to 8 carbon atoms; represent.

In some embodiments, R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ are each independently hydrogen, an alkyl group having 1 to 8 carbon atoms, or a halogen substituent having 1 to 8 carbon atoms. represents an alkyl group having

In some embodiments, Y ¹ is oxygen, sulfur, NR ¹⁸ or a bond, and R ¹⁸ is hydrogen, an alkyl group having 1 to 8 carbon atoms, 1 to 8 carbon atoms, and a halogen substituted represents an alkyl group having a group, an acyl group having 2 to 8 carbon atoms or an alkenyl group having 2 to 8 carbon atoms.

In some embodiments, A ¹ is oxygen, CH ₂ , N-NH ₂ or N-OR ¹⁹ and R ¹⁹ is hydrogen, an alkyl group having 1-8 carbon atoms, 1-8 an alkyl group having from 2 to 8 carbon atoms and a halogen substituent, an acyl group from 2 to 8 carbon atoms, an alkenyl group from 2 to 8 carbon atoms or an aryl moiety from 6 to 10 carbon atoms and from 1 to 8 carbon atoms; represents an aralkyl group having an alkylene portion of 5 carbon atoms.

In some embodiments, Q ¹ is hydrogen, halogen, hydroxyl, nitro, amino, an alkyl group having 1 to 8 carbon atoms, a 3 to 7 membered cycloalkyl group, a cycloalkyl group having 2 to 8 carbon atoms. an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and a 3 to 7-membered cycloalkyl substituent, Alkyl groups having 1 to 8 carbon atoms and halogen substituents, alkyl groups having 1 to 8 carbon atoms and alkoxy substituents having 1 to 8 carbon atoms, 1 to 8 carbon atoms and halogen Alkoxy groups with substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms or aryl moieties with 6 to 10 carbon atoms and 1 to 8 carbon atoms Represents an aralkyl group having an alkylene moiety.

In some embodiments, r is an integer from 1 to 4.

In some embodiments, s is an integer from 1 to 5.

Compounds of formula (V) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

Compounds having formula (V) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

In some embodiments, the compound of formula (V) is a compound shown in Table 10, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.16. Compounds of Formula (W) In some embodiments, compounds of the invention are compounds of Formula (W):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^２１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^２３、Ｒ^２４、Ｒ^２５およびＲ^２６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｙ^２は、酸素、硫黄、ＮＲ^２８または結合であり、Ｒ^２８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｑ^２は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
ｔは、１、２、３または４であり、
ｕは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R21 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ²² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ² is oxygen, sulfur, NR ²⁸ or a bond, R ²⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
Q ² is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
t is 1, 2, 3 or 4,
u is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

In some embodiments, R ²¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, alkyl group having 1 to 8 carbon atoms, cycloalkyl group having 3 to 7 members, cycloalkyl group having 2 to 8 alkenyl groups having carbon atoms, alkynyl groups having 2 to 8 carbon atoms, alkoxy groups having 1 to 8 carbon atoms, cycloalkyl substituents having 1 to 8 carbon atoms and 3 to 7 members; alkyl groups having 1 to 8 carbon atoms and halogen substituents; alkyl groups having 1 to 8 carbon atoms and alkoxy substituents having 1 to 8 carbon atoms; Alkoxy groups with carbon atoms and halogen substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms, 5- or 6-membered heterocyclic groups, 6 to 10 represents an aralkyl group having an aryl part of carbon atoms and an alkylene part of 1 to 8 carbon atoms, or an alkyl group having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic substituent.

In some embodiments, R ²² is hydrogen, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkenyl group having 1 to 8 carbon atoms, and a 3 to 7 membered an alkyl group having a cycloalkyl substituent, an alkyl group having 1 to 8 carbon atoms and a halogen substituent, an alkyl group having an alkoxy substituent having 1 to 8 carbon atoms and 1 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, an aryl group having 6 to 10 carbon atoms or an aralkyl group having an aryl part of 6 to 10 carbon atoms and an alkylene part of 1 to 8 carbon atoms; represent.

In some embodiments, R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are each independently hydrogen, an alkyl group having 1 to 8 carbon atoms, or a halogen substituent having 1 to 8 carbon atoms. represents an alkyl group having

In some embodiments, Y ² is oxygen, sulfur, NR ²⁸ or a bond, and R ²⁸ is hydrogen, an alkyl group having 1 to 8 carbon atoms, 1 to 8 carbon atoms, and a halogen substituted represents an alkyl group having a group, an acyl group having 2 to 8 carbon atoms or an alkenyl group having 2 to 8 carbon atoms.

In some embodiments, Q ² is hydrogen, halogen, hydroxyl, nitro, amino, an alkyl group having 1 to 8 carbon atoms, a 3 to 7 membered cycloalkyl group, a cycloalkyl group having 2 to 8 carbon atoms. an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and a 3 to 7-membered cycloalkyl substituent, Alkyl groups having 1 to 8 carbon atoms and halogen substituents, alkyl groups having 1 to 8 carbon atoms and alkoxy substituents having 1 to 8 carbon atoms, 1 to 8 carbon atoms and halogen Alkoxy groups with substituents, acyl groups with 2 to 8 carbon atoms, aryl groups with 6 to 10 carbon atoms or aryl moieties with 6 to 10 carbon atoms and 1 to 8 carbon atoms Represents an aralkyl group having an alkylene moiety.

In some embodiments, t is an integer from 1 to 4.

In some embodiments, u is an integer from 1 to 5.

Compounds having formula (W) can also exist in the form of optical isomers, such as enantiomers, or racemates, or geometric isomers, such as cis or trans. Isomers of these compounds are also provided.

Compounds having formula (W) can exist in the form of pharmaceutically acceptable salts. Examples of salts include alkali metal salts such as sodium, potassium and lithium salts.

In some embodiments, the compound of formula (W) is a compound shown in Table 11, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

5.2.17. Compounds of Formula (X) In some embodiments, compounds of the invention are compounds of Formula (X):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted with alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

In some embodiments, the compound is

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

5.2.18. Compounds of Formula (Y) In some embodiments, compounds of the invention are compounds of Formula (Y):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

5.2.19. Compounds of Formula (Z) In some embodiments, compounds of the invention are compounds of Formula (Z):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

5.2.20. Compounds of Formula (AA) In some embodiments, compounds of the invention are compounds of Formula (AA):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである
（式中、
Ｌは、（ＣＨ_２）_５であり、これは、無置換であるか、または１つのメチル基によって置換されており、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、０または１であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^３は、Ｃ_１～４ハロアルキル、ＮＯ_２、ＣＮ、ハロゲンまたはＣ（Ｏ）Ｏ（Ｃ_１～４アルキル）であり、
Ｒ^２０は、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
L is (CH ₂ ) ₅ , which is unsubstituted or substituted with one methyl group;
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 0 or 1,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
R ³ is C _1-4 haloalkyl, NO ₂ , CN, halogen or C(O)O (C _1-4 alkyl),
R ²⁰ is hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).

5.2.21. Additional Compounds In some embodiments, the compounds of the invention are:

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

In some embodiments, the compounds of the invention are

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである。
５．３．本発明の組成物

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
5.3. Composition of the invention

In some embodiments, compositions of the invention include (i) an effective amount of a compound of the invention and (ii) a pharmaceutically acceptable carrier or vehicle.

In some embodiments, compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried. In some embodiments, the compositions of the invention include (i) an effective amount of a racemate of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) Includes a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of a mixture of enantiomers of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; (ii) comprising a pharmaceutically acceptable carrier or vehicle; In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (R) - having a hydroxyl-containing allylic carbon atom with an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (R) - a hydroxyl-containing allylic carbon atom having an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle, wherein the composition comprises a (S)-enantiomer of Compound I or a pharmaceutically acceptable carrier or vehicle; Substantially free of acceptable salts thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (S) - having a hydroxyl-containing allylic carbon atom with an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (S) - a hydroxyl-containing allylic carbon atom having an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle, wherein the composition comprises an (R)-enantiomer of Compound I, or a pharmaceutically acceptable carrier or vehicle; Substantially free of acceptable salts, solvates, esters, amides or prodrugs thereof. In some embodiments, the compositions of the invention include (i) an effective amount of a non-racemic mixture of the (R)- and (S)-enantiomers of Compound I, or a pharmaceutically acceptable including a salt, solvate, ester, amide or prodrug thereof and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the non-racemic mixture has an excess of the (R)-enantiomer over the (S)-enantiomer. In some embodiments, the non-racemic mixture has an excess of the (S)-enantiomer over the (R)-enantiomer.

In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition being substantially free of the (E)-isomer of Compound I or a pharmaceutically acceptable salt thereof. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a (Z)-isomer of Compound I, or a pharmaceutically acceptable salt, solvate, ester, amide or Substantially free of prodrugs. In some embodiments, the compositions of the invention include (i) an effective amount of a non-equivalent mixture of the (Z)- and (E)-isomers of Compound I, or a pharmaceutically acceptable including a salt, solvate, ester, amide or prodrug and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the unequal mixture has an excess of the (Z)-isomer over the (E)-isomer. In some embodiments, the unequal mixture has an excess of the (E)-isomer over the (Z)-isomer.

In some embodiments, compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (Z) - isomers and have a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (Z) - isomer and has a hydroxyl-containing allyl carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((Z)- (S)-I), ((E)-(R)-I) or ((E)-(S)-I), or a pharmaceutically acceptable salt thereof. In some embodiments, compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (Z) - isomers and have a hydroxyl-containing allylic carbon atom with (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (Z) - isomer and has a hydroxyl-containing allylic carbon atom having (S)-stereochemistry); and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((Z)- (R)-I), ((E)-(R)-I) or ((E)-(S)-I), or a pharmaceutically acceptable salt thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (E) - isomers and have a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (E) -isomer and having a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((E)-( S)-I), ((Z)-(R)-I) or ((Z)-(S)-I), or a pharmaceutically acceptable salt thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (E) - isomers and have a hydroxyl-containing allylic carbon atom with (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound I or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound I is (E) - isomer and has a hydroxyl-containing allylic carbon atom having an (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((E)- (R)-I), ((Z)-(R)-I) or ((Z)-(S)-I), or a pharmaceutically acceptable salt thereof.

In some embodiments, compositions of the invention include (i) an effective amount of Compound II or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried. In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound II, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound II, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition being substantially free of the (E)-isomer of Compound II or a pharmaceutically acceptable salt thereof. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound II, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound II, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition being substantially free of the (Z)-isomer of Compound II or a pharmaceutically acceptable salt thereof. In some embodiments, compositions of the invention include (i) an effective amount of a non-equivalent mixture of the (Z)- and (E)-isomers of Compound II, or a pharmaceutically acceptable including a salt, solvate, ester, amide or prodrug and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the unequal mixture has an excess of the (Z)-isomer over the (E)-isomer. In some embodiments, the unequal mixture has an excess of the (E)-isomer over the (Z)-isomer.

In some embodiments, compositions of the invention include (i) an effective amount of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried. In some embodiments, the compositions of the invention include (i) an effective amount of a racemate of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) Includes a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of a mixture of enantiomers of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; (ii) comprising a pharmaceutically acceptable carrier or vehicle; In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (R) - having a hydroxyl-containing allylic carbon atom with an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (R) - a hydroxyl-containing allylic carbon atom having an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle, wherein the composition comprises an (S)-enantiomer of Compound III or a pharmaceutically acceptable carrier or vehicle; Substantially free of acceptable salts thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (S) - having a hydroxyl-containing allylic carbon atom with an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (S) - a hydroxyl-containing allylic carbon atom having an enantiomer), and (ii) a pharmaceutically acceptable carrier or vehicle, wherein the composition comprises an (R)-enantiomer of Compound III, or a pharmaceutically acceptable carrier or vehicle; Substantially free of acceptable salts, solvates, esters, amides or prodrugs thereof. In some embodiments, compositions of the invention include (i) an effective amount of a non-racemic mixture of the (R)- and (S)-enantiomers of Compound III, or a pharmaceutically acceptable including a salt, solvate, ester, amide or prodrug thereof and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the non-racemic mixture has an excess of the (R)-enantiomer over the (S)-enantiomer. In some embodiments, the non-racemic mixture has an excess of the (S)-enantiomer over the (R)-enantiomer.

In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (Z)-isomer of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition being substantially free of the (E)-isomer of Compound III or a pharmaceutically acceptable salt thereof. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, compositions of the invention include (i) an effective amount of the (E)-isomer of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; , and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a (Z)-isomer of Compound III, or a pharmaceutically acceptable salt, solvate, ester, amide or Substantially free of prodrugs. In some embodiments, the compositions of the invention include (i) an effective amount of a non-equivalent mixture of the (Z)- and (E)-isomers of Compound III, or a pharmaceutically acceptable including a salt, solvate, ester, amide or prodrug and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the unequal mixture has an excess of the (Z)-isomer over the (E)-isomer. In some embodiments, the unequal mixture has an excess of the (E)-isomer over the (Z)-isomer.

In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (Z) - isomers and have a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (Z) - isomer and has a hydroxyl-containing allyl carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((Z)- (S)-III), ((E)-(R)-III) or ((E)-(S)-III), or a pharmaceutically acceptable salt thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (Z) - isomers and have a hydroxyl-containing allylic carbon atom with (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (Z) - isomer and has a hydroxyl-containing allylic carbon atom having (S)-stereochemistry); and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((Z)- (R)-III), ((E)-(R)-III) or ((E)-(S)-III), or a pharmaceutically acceptable salt thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (E) - isomers and have a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (E) - isomer and has a hydroxyl-containing allylic carbon atom having an (R)-stereochemistry), (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound (E)-(S )-III), ((Z)-(R)-III) or ((Z)-(S)-III), or a pharmaceutically acceptable salt thereof. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (E) - isomers and have a hydroxyl-containing allylic carbon atom with (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle. In some embodiments, the compositions of the invention include (i) an effective amount of Compound III or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Compound III is (E) - isomer and has a hydroxyl-containing allylic carbon atom having an (S)-stereochemistry), and (ii) a pharmaceutically acceptable carrier or vehicle, the composition comprising a compound ((E)- (R)-III), ((Z)-(R)-III) or ((Z)-(S)-III), or a pharmaceutically acceptable salt thereof.

In some embodiments, compositions of the invention include (i) an effective amount of Compound IV or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable carrier or vehicle.

In some embodiments, compositions of the invention include (i) an effective amount of Compound V or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, compositions of the invention include (i) an effective amount of Compound VI or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, compositions of the invention include (i) an effective amount of Compound VIa, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, compositions of the invention include (i) an effective amount of Compound VIb, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, compositions of the invention include (i) an effective amount of Compound VII or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, compositions of the invention include (i) an effective amount of Compound VIII or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; and (ii) a pharmaceutically acceptable including the carrier or vehicle in which it is carried.

In some embodiments, the compositions of the invention further include another therapeutically active agent.

A composition of the invention that further comprises another therapeutically active agent is a "combination of the invention." The invention provides a combination of the invention. The combinations of the invention can include one or more therapeutically active agents.

In some embodiments, other therapeutically active agents include lipid-lowering drugs, statins, cholesterol absorption inhibitors, antibodies to PCSK9, siRNA PCSK9, anti-fibrotic agents, thyroid hormones, selective thyroid receptor-β agonists, apoptosis A signal-regulated kinase 1 (ASK1) inhibitor, an acetyl-CoA carboxylase (ACC) inhibitor, an integrin antagonist or a non-steroidal farnesoid X receptor (FXR) agonist.

In some embodiments, the lipid-lowering drug is gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate, clinofibrate, etofylline, pyrifibrate, simfibrate, tocofibrate or pemafibrate. In some embodiments, the lipid-lowering drug is gemfibrozil, fenofibrate, bezafibrate or pemafibrate.

In some embodiments, the statin is atorvastatin, simvastatin, pravastatin, rosuvastatin, fluvastatin, lovastatin, pitavastatin, mevastatin, davastatin, dihydrocompactin or cerivastatin, or a pharmaceutically acceptable salt or solvate thereof. be. In some embodiments, the statin is atorvastatin, simvastatin, pravastatin or rosuvastatin, or a pharmaceutically acceptable salt or solvate thereof.

In some embodiments, the cholesterol absorption inhibitor is ezetimibe.

In some embodiments, the antibody against PCSK9 is evolocumab alirocumab, bococizumab, 1D05-IgG2 (Merck), RG7652 (Genentech), LY3015014 (Eli Lilly) or LGT-209 (Novartis/Cyon Therapeutics) . In some embodiments, the antibody against PCSK9 is evolocumab or alirocumab.

In some embodiments, siRNA PCSK9 is an siRNA that interferes with the production of PCSK9, such as inclisiran.

In some embodiments, the antifibrotic agent is nitazoxamide, tizoxanide or tizoxanide glucuronide, nintedanib, imatinib, or a pharmaceutically acceptable salt or solvate thereof.

In some embodiments, the selective thyroid receptor-β agonist is VK2809 (Viking Therapeutics), MGL-3196 (Madrigal Pharmaceuticals), MGL-3745 (Madrigal Pharmaceuticals), SKL-1476 3. Sobetilome, BCT304 (ITL Pharma) , ZYT1 (Zydus Cadila), MB-0781 (Metabasis) or Eprotylome.

In some embodiments, the ASK1 inhibitor is selonsertib.

In some embodiments, the ACC inhibitor is fircosostat.

In some embodiments, the integrin antagonist is an α5β1 inhibitor or a pan-integrin inhibitor. In some embodiments, the integrin antagonist is IDL-2965 (Indalo Therapeutics). In some embodiments, the integrin antagonist is CLT-28643 (ClanoTech AB).

In some embodiments, the integrin antagonist is 3-(6-methoxypyridin-3-yl)-3-(4-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2 --yl)propyl)-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyridin-3-yl)-3-(4-(2-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-2-(((benzyloxy)carbonyl)amino)-3 -(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-2H-indazol-2-yl)propanoic acid; 3-phenyl-3-(5 -(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(6-methoxypyridine) -3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-2H-indazol-2-yl)propanoic acid; ( S)-3-(6-methoxypyridin-3-yl)-3-(6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-2H- indazol-2-yl)propanoic acid; (S)-3-(6-methoxypyridin-3-yl)-3-(6-((2-methyl-5,6,7,8-tetrahydro-1,8 -naphthyridin-3-yl)methyl)-2H-indazol-2-yl)propanoic acid; (S)-3-(6-methoxypyridin-3-yl)-3-(6-(3-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-2H-indazol-2-yl)propanoic acid; (S)-3-(6-methoxypyridin-3-yl)-3- (6-(2-(2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)ethyl)-2H-indazol-2-yl)propanoic acid; 3-(6- methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)pyrazolo[4,3-b]pyridine- 1-yl)propanoic acid; 3-(5-(2-((4,5-dihydroimidazol-2-yl)amino)ethoxy)-1H-indazol-1-yl)-3-(6-methoxypyridine- 3-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl-)-2 -((2,4,6-trimethylphenyl)sulfonamido)propanoic acid; 2-(((benzyloxy)carbonyl)amino)-3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(quinoxalin-2-yl)-3-(5-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (R)-3-(quinoxalin-2-yl)-3-(5-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl-)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(quinoxalin-2-yl)-3 -(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl-)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3,5- dichlorophenyl)-3-(4-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-propyl)-1H-indazol-1-yl)propanoic acid; 3-( quinoxalin-2-yl)-3-(4-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyridin-3-yl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-indazole- 1-yl)propanoic acid; 3-(3,5-dichlorophenyl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-propyl)- 1H-indazol-1-yl)propanoic acid; 3-(quinoxalin-2-yl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) propyl)-1H-indazol-1-yl)propanoic acid; 3-(3-(dimethylcarbamoyl)phenyl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridine) -2-yl)propyl)-1H-indazol-1-yl)propanoic acid; 3-(3-(dimethylcarbamoyl)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propanoic acid; 3-(dibenzo[b,d]furan-3-yl)-3-(5-(2-(5 , 3-(3-((dimethylamino)methyl)phenyl)-3 -(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propanoic acid; 3-(quinoxalin-2-yl) )-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propanoic acid; 5-dichlorophenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-ethyl)-1H-indazol-1-yl)propanoic acid; 3 -(3-(dimethylcarbamoyl)phenyl)-3-(4-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl ) Propanoic acid; 3-(dibenzo[b,d]furan-3-yl)-3-(4-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethoxy)-1H-indazol-1-yl)propanoic acid; 6,6,6-trifluoro-3-(4-(3-(5,6,7,8-tetrahydro-1,8-naphthyridine-2- yl)propyl)--1H-indazol-1-yl)hexanoic acid; 3-(3,5-dichlorophenyl)-3-(4-(2-(5,6,7,8-tetrahydro-1,8- naphthyridin-2-yl)-ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(quinoxalin-2-yl)-3-(4-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyridin-3-yl)-3-(5-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3-(dimethylcarbamoyl)phenyl)-3-(5-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-2-(((benzyloxy)carbonyl) (R)- 3-(3-(dimethylcarbamoyl)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole-1- (S)-3-(3-(dimethylcarbamoyl)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)) ethoxy)-1H-indazol-1-yl)propanoic acid; 2-(((benzyloxy)carbonyl)amino)-3-(4-(2-(5,6,7,8-tetrahydro-1,8- (R)-3-(6-methoxypyridin-3-yl)-3-(5-(2-(5,6, (S)-3-(6-methoxypyridin-3-yl)-3-(7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-chloropyridin-3- yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; ,5-dichlorophenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3-fluoro-4-methoxyphenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole- 1-yl)propanoic acid; 3-cyclopropyl-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1-H-indazole- 1-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl-)octanoic acid ;3-(2,3-dihydrobenzofuran-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H- indazol-1-yl)propanoic acid; 3-(quinolin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy) -1H-indazol-1-yl)propanoic acid (48); 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole -1-yl-)-3-(thiophen-2-yl)propanoic acid; 3-(pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1, 8-Naphthyridin-2-yl)ethoxy-)-1H-indazol-1-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)ethoxy)-1H-indazol-1-yl-)propanoic acid; 3-(3-cyanophenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine) -2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-fluoropyridin-2-yl)-3-(5-(2-(5,6,7,8-tetrahydro) -1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(dibenzo[b,d]furan-2-yl)-3-(5-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(4,6-dimethylpyrimidin-2-yl)- 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(2-methylbenzo[ d] Thiazol-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propane Acid; 3-(4-phenoxyphenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl ) Propanoic acid; 3-(3-morpholinophenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-ethoxy)-1H-indazole- 1-yl)propanoic acid; 3-(3-(1H-pyrrol-1-yl)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine) 2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3-((dimethylamino)methyl)phenyl)-3-(5-(2-(5,6,7,8- Tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(pyridin-2-yl)-3-(5-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy-)-1H-indazol-1-yl)propanoic acid; 3-(3-(2-oxopyrrolidin-1-yl)phenyl)-3- (5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(1-propylpyrazole-4 -yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S) -3-(6-methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-2H-indazole- (S)-3-(6-methoxypyridin-3-yl)-3-(6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) -yl)ethoxy)-2H-indazol-2-yl)propanoic acid; 3-(2-methylpyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(6-methoxypyridin-3-yl)-3-(5-(3-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-2H-indazol-2-yl)propanoic acid; 3-(3-(3,5-dimethylpyrazol-1-yl) ) phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 4-( 4-(benzyloxy)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl-)ethoxy)-1H-indazol-1-yl) Butanoic acid; 3-(6-methoxypyridin-3-yl)-3-(3-methyl-5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy) )-1H-indazol-1-yl)propanoic acid; 3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-(5-(2-(5,6,7, 8-tetrahydro-1,-8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (3S)-3-(6-methoxypyridin-3-yl)-3-(6 -(2-(1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-2H-indazol-2-yl)propanoic acid; 4-phenyl-2-((5-( 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)methyl)butanoic acid; 3-(1-(tert-butoxycarbonyl) piperidin-4-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid ;3-(pyridin-4-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy-)-1H-indazole-1- yl)propanoic acid; 2-(1-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)cyclo 3-(2-ethoxypyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)- 1H-indazol-1-yl)propanoic acid; 4-(4-fluorophenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy) )-1H-indazol-1-yl)butanoic acid; 3-(5-methoxypyrazin-2-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine) -2--yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(quinoxalin-6-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1) ,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(quinolin-3-yl)-3-(6-(2-(5,6, (S)-3-(6-((2-methyl-5,6,7 ,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-2H-indazol-2-yl)-3-(quinolin-3-yl)propanoic acid; (3S)-3-(quinoline-3- (S) -3-(3-(2-oxopyrrolidin-1-yl)phenyl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy) -1H-indazol-1-yl)propanoic acid; (R)-3-(3-(2-oxopyrrolidin-1-yl)phenyl)-3-(5-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-fluoro-6-methoxypyridin-3-yl)-3-(5-( 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(quinolin-3-yl) -3-(6-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-2H-indazol-2-yl)propanoic acid; (3S)-3- (quinolin-3-yl)-3-(6-(3-(1,2,3,4-tetrahydro-1,8-naphthyridin-2-yl)-propyl)-2H-indazol-2-yl)propane Acid; 3-(5-(hydroxymethyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)- 1H-indazol-1-yl)propanoic acid; 3-(6-(2-hydroxy-2-methylpropoxy)-5-methylpyridin-3-yl)-3-(5-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3,4-dihydro-2H-pyrido[3,2-b][ 1,4]oxazin-6-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl ) Propanoic acid; 3-(2-methoxypyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)- 1H-indazol-1-yl)propanoic acid; 3-(2-(2-oxopyrrolidin-1-yl)pyridin-4-yl)-3-(5-(2-(5,6,7,8- 3-(isoquinolin-6-yl)-3-(5-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(pyrido[2,3-b]pyrazin-7-yl)-3- (5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(1,8-naphthyridin- 2-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3 -(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1 ,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-2-(((benzyloxy)carbonyl)amino)-3-(5-((5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)methoxy)-2H-indazol-2-yl)propanoic acid; (R)-3-(5-(hydroxymethyl)pyridin-3-yl) -3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3- (5-(hydroxymethyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole- 1-yl)propanoic acid; 3-(1,8-naphthyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ) ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(2-oxopyrrolidin-1-yl)pyridin-3-yl)-3-(5-(2-(5,6, 7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl-)-3-(1-(tetrahydro-2H-pyran-2-yl)pyrazolo[3,4-b]pyridine-5 -yl)propanoic acid; 3-(5-(1,3-dioxolan-2-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1- ,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-((dimethylamino)methyl)pyridin-3-yl)-3-(5-(2- (5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(1H-pyrazolo[3,4-b]pyridine -5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; ( S) -3-(2-ethoxypyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H- indazol-1-yl)propanoic acid; (R)-3-(2-ethoxypyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine) -2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)-3- (5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(benzo[d]thiazole- 6-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3- (2-morpholinopyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl ) Propanoic acid; 3-(2-(methylamino)pyrimidin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy )-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyridin-3-yl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridine) -2--yl)propyl)-1H-pyrazolo[4,3-b]pyridin-1-yl)propanoic acid; 3-(6-methoxypyridazin-3-yl)-3-(5-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1
H-indazol-1-yl)propanoic acid; 3-([1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(5-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2- yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-( 1-Methyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1-,8-naphthyridin-2-yl) )ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(2-methoxypyrimidin-5-yl)-3-(6-(2-(5,6,7,8-tetrahydro -1,8-naphthyridin-2-yl)ethyl)-2H-indazol-2-yl)propanoic acid; 3-(2-(azetidin-1-yl)pyrimidin-5-yl)-3-(5-( 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(2-methyl-2H-pyrazolo[3, 4-b]pyridin-5-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1-,8-naphthyridin-2-yl)ethoxy)-1H-indazole-1- yl)propanoic acid; 3-(5-(oxazol-5-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) -yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(7-ethyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)-3- (5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-((( tert-butoxycarbonyl)amino)methyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H -indazol-1-yl)propanoic acid; 3-(5-morpholinopyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine--2) -yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(methylsulfonyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8- Tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)- 3-(5-(2-(5,6,7,8-tetrahydro-1,-8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-( pyrrolidin-1-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole-1 -yl)propanoic acid; (R)-3-(pyrido[2,3-b]pyrazin-7-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8 -naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(pyrido[2,3-b]pyrazin-7-yl)-3-(5-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-([1,2,4]triazolo[4, 3-a]pyridin-7-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl ) Propanoic acid; 3-(5-(aminomethyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy )-1H-indazol-1-yl)propanoic acid; 3-([1,3]dioxolo[4,5-b]pyridin-6-yl)-3-(5-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(1,3-dioxolan-2-yl)-6-methoxypyridine) -3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3 -(6-(1H-pyrazol-1-yl)pyridin-2-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy )-1H-indazol-1-yl)propanoic acid; 3-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)-3-(5-(2-(5,6,7, 8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(2-methyl-2H-pyrazolo[4,3-b]pyridin-6-yl )-3-(5-(2-(5,6,7,8-tetrahydro-1-,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(1 -Methyl-1H-pyrazolo[4,3-b]pyridin-6-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1-,8-naphthyridin-2-yl) (R)-3-(5-(1,3-dioxolan-2-yl)pyridin-3-yl)-3-(5-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(5-(1,3-dioxolane) -2-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazole-1 -yl)propanoic acid; 3-(1-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1 ,-8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(1H-pyrazol-5-yl)pyridin-3-yl)-3-(5- (2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(6-morpholinopyrazin-2-yl) -3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5- (1-Methyl-1H-pyrazol-4-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(2-hydroxypropan-2-yl)pyridin-3-yl)-3-(5-(2-(5,6,7 ,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (R)-3-(5-(2-hydroxypropan-2-yl)pyridine) -3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(5-(2-hydroxypropan-2-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8- (R)-3-(2-methoxypyrimidin-5-yl)-3-(5-(2-(5,6, (S)-3-(2-methoxypyrimidin-5-yl)-3-( 5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(6-methoxypyrazine-2- (R) -3-(5-(2-oxopyrrolidin-1-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2) -yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(5-(2-oxopyrrolidin-1-yl)pyridin-3-yl)-3-(5-(2 -(5,6,7,8-tetrahydro--1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(morpholine-4-carbonyl)pyridine -3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(dimethylcarbamoyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H- indazol-1-yl)propanoic acid; 3-(5-(4-methylpiperazine-1-carbonyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-cyclopropylpyridin-3-yl)-3-(5-(2-(5,6 ,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(4-methylpiperazin-1-yl)pyridin-3- yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,-8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-( 5-(azetidine-1-carbonyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H -indazol-1-yl)propanoic acid; 3-(5-((2-(dimethylamino)ethyl)carbamoyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8 -tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(2-methylpyrimidin-5-yl)-3-(5-( 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (R)-3-(2-methylpyrimidine-5 -yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-( 5-(1H-pyrazol-1-yl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)- 1H-indazol-1-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl -) Hexanoic acid; 3-(5-(dimethylamino)pyridin-3-yl)-3-(5-(2(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy )-1H-indazol-1-yl)propanoic acid; 3-cyclohexyl-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H --indazol-1-yl)propanoic acid; (R)-3-(5-(methylsulfonyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro- 1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(5-(methylsulfonyl)pyridin-3-yl)-3-(5-( 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(((methoxycarbonyl)amino) ) methyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl) Propanoic acid; (R)-3-(5-(((methoxycarbonyl)amino)methyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1, 8-Naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; (S)-3-(5-(((methoxycarbonyl)amino)methyl)pyridin-3-yl)-3- (5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 3-(5-(methylsulfonamide) methyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1-,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl) Propanoic acid; 3-(5-(acetamidomethyl)pyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy) -1H-indazol-1-yl)propanoic acid; 3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1- yl-)-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)propanoic acid; 4-((6-(2-carboxy-1-(5-(2-( 5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy-)-1H-indazol-1-yl)ethyl)pyrazin-2-yl)amino)butanoic acid; 3-(6- methoxypyridin-3-yl)-3-(4-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propane Acid; (R)-3-(5-(2-((R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy-)-1H-indazole -1-yl)-3-(2-methylpyrimidin-5-yl)propanoic acid; (S)-3-(5-(2-((R)-7-methyl-5,6,7,8- (R)-3-(5-( 2-((S)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy-)-1H-indazol-1-yl)-3-(2-methyl pyrimidin-5-yl)propanoic acid; (S)-3-(5-(2-((S)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) 3-(6-methoxypyridin-3-yl)-3-(5-(2-( (S)-3-(1-methyl-1,2,3,4-tetrahydropyrido[2,3--b]pyrazin-6-yl)ethoxy)-1H-indazol-1-yl)propanoic acid; 5-(2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)ethoxy)-1H-indazol-1-yl)-3-(6- methoxypyridin-3-yl)propanoic acid; and (R)-3-(5-(2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl) ) ethoxy)-1H-indazol-1-yl)-3-(6-methoxypyridin-3-yl)propanoic acid; or a pharmaceutically acceptable salt thereof. See US Patent Application Publication No. 2019/0256496, which is incorporated herein by reference in its entirety.

In some embodiments, the integrin antagonist is (S)-3-(3-(2-methoxyethoxy)phenyl)-4-((R)-3-(2-(5,6,7,8- Tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-3-(3-((R)-2-methoxypropoxylphenyl)-4-((R )-3-(2-(5,6,7,8-tetrahydro-1,-8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-3-(3-( (S)-2-Methoxypropoxylphenyl)-4-4R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidine-1- (S)-3-(3-(2-methoxy-2-methylpropoxy)phenyl)-44(R)-3-(2-(5,6,7,8-tetrahydro-1, 8-Naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; 3-(3-(((S)-1-methoxypropan-2-yl)oxy)phenyl)-4-((R) -3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-4-((R)-3 -(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(((S)-tetrahydrofuran-3-yl) )oxy)phenyl)butanoic acid; (S)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidine-1 -yl)-3-(3-(((R)-tetrahydrofuran-3-yl)oxy)phenyl)butanoic acid; (S)-3-(3,5-bis(2-methoxyethoxy)phenyl)-4 -((R)-3-(2-(5,6,7,8-tetrahydro-1,-8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (3S)-4- ((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(tetrahydrofuran-3- yl) phenylbutanoic acid; (3S)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl )-3-(3-(tetrahydrofuran-3-yl)phenylbutanoic acid; (S)-3-(3-((1-methoxy-2-methylpropan-2-yl)oxy)phenyl)-4-4R )-3-(2-(5,6,7,8--tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-3-(3-( ((R)-1-methoxypropan-2-yl)oxy)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine-2- yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-3-(3-(2-isopropoxyethoxy)phenyl)-4-((R)-3-(2-(5,6,7 ,8-tetrahydro-1,8--naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; (S)-4-((R)-3-(2-(5,6,7, 8-Tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(((R)-tetrahydrofuran-2-yl)methoxy)phenyl)butanoic acid; (S) -4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(( (S)-tetrahydrofuran-2-yl)methoxy)phenyl)butanoic acid; (S)-3-(2-fluoro-5-(2-methoxyethoxy)phenyl)-4-((R)-3-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; 3-(3-((1,3-dimethoxypropan-2-yloxy) ) phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; 3- (3-(2-fluoroethoxy)-5-(2-methoxyethoxy)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridine- 2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; 3-(3-(3-methoxypropoxy)phenyl)-4-((R)-3-(2-(5,6,7,8- tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; or 3-(3-(oxetan-3-ylmethoxy)phenyl)-4-((R)-3-(2 -(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic acid; or a pharmaceutically acceptable salt thereof. See US Patent Application Publication No. 2019/0112306, which is incorporated herein by reference in its entirety.

In some embodiments, the integrin antagonist has the structure

または薬学的に許容されるその塩を有する。その全体が参照により本明細書に組み込まれている、米国特許第１０，２１４，５２２号明細書を参照されたい。

or a pharmaceutically acceptable salt thereof. See US Pat. No. 10,214,522, which is incorporated herein by reference in its entirety.

In some embodiments, the integrin antagonist has the structure

または薬学的に許容されるその塩を有する。その全体が参照により本明細書に組み込まれている、米国特許出願公開第２０１８／００７２６８４号明細書を参照されたい。

or a pharmaceutically acceptable salt thereof. See US Patent Application Publication No. 2018/0072684, which is incorporated herein by reference in its entirety.

In some embodiments, the nonsteroidal farnesoid X receptor (FXR) agonist is cilofexor.

In some embodiments, the combination of the invention comprises selonsertib, filsocostat or cilofexor. In some embodiments, the combination of the invention comprises selonsertib and filsocostat. In some embodiments, the combination of the invention comprises selonsertib and cilofexor. In some embodiments, the combination of the invention includes filcosostat and cilofexor. In some embodiments, the combination of the invention comprises selonsertib, filsocostat and cilofexor.

In some embodiments, pharmaceutically acceptable carriers or vehicles include, but are not limited to, binders, fillers, diluents, disintegrants, wetting agents, lubricants, glidants, colorants. , dye transfer inhibitors, sweetening or flavoring agents.

Binders or granulating agents impart cohesive properties to the tablet to ensure that it remains intact after compression. Suitable binders or granulating agents include, but are not limited to, starches such as corn starch, potato starch and pregelatinized starch (e.g. STARCH 1500); gelatin; sugars such as sucrose, glucose, dextrose, molasses and lactose; acacia. , alginic acid, alginate, extract of Irish moss, Panwar gum, ghatti gum, mucilage of isabgol husks, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone (PVP), vegum, larch Natural and synthetic gums such as larch arabogalactan, powdered tragacanth and guar gum; ethylcellulose, cellulose acetate, calcium carboxymethylcellulose, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose ( microcrystalline celluloses such as AVICEL-PH-101, AVICEL-PH-103, AVICEL RC-581, AVICEL-PH-105 (FMC Corp., Marcus Hook, PA); and mixtures thereof. .

Suitable fillers include, but are not limited to, talc, calcium carbonate, microcrystalline cellulose, powdered cellulose, dextrate, kaolin, mannitol, silicic acid, sorbitol, starch, pregelatinized starch, and mixtures thereof. In some embodiments, the binder is hydroxypropyl cellulose.

The binder or filler can be present from about 2% to about 49% by weight of the inventive compositions provided herein, or any range within these values. In some embodiments, the binder or filler is present in the compositions of the present invention at about 5% to about 15% by weight. In some embodiments, the binder or filler is present in the compositions of the invention at about 5%, about 6%, about 7%, about 8%, about 9%, about 8% by weight. %, about 10%, about 11%, about 12%, about 13%, about 14% or about 15%, or any range within any of these values.

Suitable diluents include, but are not limited to, dicalcium phosphate, calcium sulfate, lactose, sorbitol, sucrose, inositol, cellulose, kaolin, mannitol, sodium chloride, dry starch and powdered sugar. Certain diluents, such as mannitol, lactose, sorbitol, sucrose and inositol, when present in sufficient quantities, can to some extent impart properties to compressed tablets that enable them to disintegrate in the mouth by chewing. can. Such compressed tablets can be used as chewable tablets. In some embodiments, the diluent is lactose monohydrate. In some embodiments, the diluent is Fast-Flo316NF, which is lactose monohydrate.

Compositions of the invention can include a diluent, for example, from about 5% to about 49%, or any range between any of these values, by weight of the composition. In some embodiments, the diluent is present in the compositions of the invention at about 15% to about 30% by weight. In some embodiments, the diluent is present in the compositions of the invention at about 15%, about 16%, about 17%, about 18%, about 19%, about 18%, about 20% by weight, about 21% by weight, about 22% by weight, about 23% by weight, about 24% by weight, about 25% by weight, about 26% by weight, about 27% by weight, about 28% by weight, about 29% by weight or about 30% by weight, or any range within either of these values.

Suitable disintegrants include, but are not limited to, agar; bentonite; celluloses such as methylcellulose and carboxymethylcellulose; wood products; sponges; cation exchange resins; alginic acid; gums such as guar gum and vegum HV; citrus pulp; Cross-linked celluloses such as calomellose; cross-linked polymers such as crospovidone; cross-linked starches; calcium carbonate; microcrystalline celluloses such as sodium starch glycolate; polacrilin potassium; starches such as corn starch, potato starch, tapioca starch and pregelatinized starch; Includes clay; align; and mixtures thereof. The amount of disintegrant in the compositions of the invention can vary. In some embodiments, the disintegrant is croscarmellose sodium. In some embodiments, the disintegrant is croscarmellose sodium NF (Ac-Di-Sol).

Compositions of the invention can include a disintegrant, for example, from about 0.5% to about 15%, or from about 1% to about 10%, by weight. In some embodiments, the compositions of the invention include about 5%, about 6%, about 7%, about 8%, about 9%, about 8%, about 10%, by weight of the composition. %, about 11%, about 12%, about 13%, about 14% or about 15% by weight, or any range within any of these values, of a disintegrant. .

Suitable lubricants include, but are not limited to, calcium stearate; magnesium stearate; mineral oil; light mineral oil; glycerin; sorbitol; mannitol; glycols such as glycerol behenate and polyethylene glycol (PEG); stearic acid; Sodium lauryl sulfate; talc; hydrogenated vegetable oils, including peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, corn oil, and soybean oil; zinc stearate; ethyl oleate; ethyl laurate; agar; starch; 200 (W.R. Grace Co., Baltimore, MD) and CAB-O-SIL® (Cabot Co. of Boston, Mass.); and mixtures thereof. In some embodiments, the lubricant is magnesium stearate.

Compositions of the invention can include a lubricant, for example, from about 0.1 to about 5% by weight of lubricant. In some embodiments, the compositions of the invention are about 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 0. .8% by weight, 1.0% by weight, 1.1% by weight, 1.2% by weight, 1.3% by weight, 1.4% by weight, 1.5% by weight, 1.6% by weight, 1.7 Weight%, 1.8% by weight, 1.9% by weight, 2.0% by weight, 2.1% by weight, 2.2% by weight, 2.3% by weight, 2.4% by weight, 2.5% by weight , 2.6%, 2.7%, 2.8%, 2.9% or 3.0% by weight, or any range within any of these values. Contains agents.

Suitable glidants include colloidal silicon dioxide, CAB-O-SIL® (Cabot Co. of Boston, Mass.), and talc, including asbestos-free talc.

Colorants include any of the approved, certified water-soluble FD&C dyes and water-insoluble FD&C dyes suspended on hydrated alumina and lake pigments, and mixtures thereof.

Flavoring agents include natural flavors extracted from plants such as fruits, as well as synthetic blends of compounds that provide a pleasant taste, such as peppermint and methyl salicylate.

Sweeteners include sucrose, lactose, mannitol, syrup, glycerin, sucralose, and artificial sweeteners such as saccharin, stevioside (stevia) and aspartame.

Suitable emulsifiers include gelatin, acacia, tragacanth, bentonite and polyoxyethylene sorbitan monooleate (TWEEN® 20), polyoxyethylene sorbitan monooleate 80 (TWEEN® 80) and trioleate. Includes surfactants such as ethanolamine. Suspending and dispersing agents include sodium carboxymethylcellulose, pectin, tragacanth, vegum, acacia, sodium carbomethylcellulose, hydroxypropylmethylcellulose, and polyvinylpyrrolidone. Preservatives include glycerin, methyl and propylparaben, benzoic acid, sodium benzoate and alcohol. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, and polyoxyethylene lauryl ether.

Solvents include glycerin, sorbitol, ethyl alcohol and syrup.

Examples of non-aqueous liquids utilized in emulsions include mineral oil and cottonseed oil. Organic acids include citric acid and tartaric acid. Carbon dioxide sources include sodium bicarbonate and sodium carbonate.

Compounds of the invention and compositions of the invention may be administered by a variety of means, including orally, parenterally, by inhalation spray, topically or rectally, in formulations containing pharmaceutically acceptable carriers, adjuvants and vehicles. may be formulated for administration by. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, and arterial injection by various injection techniques. Intra-arterial and intravenous injection as used herein includes administration by catheter.

Compounds of the invention and compositions of the invention may be formulated according to conventional procedures appropriate to the desired route of administration. Accordingly, the compositions of the invention may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, including suspending, stabilizing and/or dispersing agents, and the like. It can contain active agents. Compounds of the invention and compositions of the invention may be formulated as preparations suitable for implantation or injection. Thus, for example, the compositions of the invention may be combined with suitable polymeric or hydrophobic substances (e.g., as emulsions in acceptable oils) or ion exchange resins, or as sparingly soluble derivatives (e.g., as sparingly soluble (as a weak salt). The compounds of the invention and compositions of the invention can be in powder form for reconstitution with a suitable vehicle, eg, sterile pyrogen-free water, before use. Formulations suitable for each of these methods of administration can be found, for example, in Remington: The Science and Practice of Pharmacy, A. Gennaro, ed., 20th edition, Lippincott, Williams & Wilkins, Philadelphia, PA.

In some embodiments, compositions of the invention are suitable for oral administration. These compositions can include solid, semi-solid, gel matrix or liquid dosage forms suitable for oral administration. As used herein, oral administration includes buccal, suplingual and sublingual administration. Suitable oral dosage forms include, but are not limited to, tablets, capsules, pills, troches, lozenges, pastels, cachets, pellets, medicinal chews, granules, bulk powders, effervescent or non-effervescent powders or granules, solutions, emulsions, suspensions, solutions, wafers, sprinkles, elixirs, syrups, or any combination thereof. In some embodiments, compositions of the invention suitable for oral administration are in the form of tablets or capsules. In some embodiments, the composition of the invention is in the form of a tablet. In some embodiments, the compositions of the invention are in the form of capsules. In some embodiments, a compound of the invention is contained in a capsule.

In some embodiments, the capsule is an immediate release capsule. A non-limiting example of a capsule is a coni-snap® hard gelatin capsule.

The compositions of the invention can be in the form of compressed tablets, powdered tablets, chewable lozenges, fast-dissolving tablets, multiple compressed tablets, or enteric-coated, sugar-coated, or film-coated tablets. Enteric-coated tablets are compressed tablets coated with a substance that is resistant to the action of stomach acid, but dissolves or disintegrates in the intestines, thus protecting the active ingredient from the acidic environment of the stomach. Enteric coating agents include, but are not limited to, fatty acids, fats, phenyl salicylates, waxes, shellac, ammoniated shellac, and cellulose acetate phthalates. Sugar-coated tablets are compressed tablets surrounded by a sugar coating that masks unpleasant tastes or odors and can be beneficial in protecting the tablet from oxidation. Film-coated tablets are compressed tablets covered by a thin layer or film of water-soluble material. Film coating agents include, but are not limited to, hydroxyethylcellulose, sodium carboxymethylcellulose, polyethylene glycol 4000, and cellulose acetate phthalate. Film coatings can impart the same general properties as sugar coatings. Multi-compressed tablets are compressed tablets made by more than one compression cycle, including layered tablets and compressed or dry-coated tablets.

In some embodiments, the coating is a film coating. In some embodiments, the film coating comprises Opadry White and Simethicone Emulsion 30% (US Pharmacopeia).

In some embodiments, a compound of the invention is contained in a tablet. In some embodiments, the compounds of the invention are contained in compressed tablets. In some embodiments, the compounds of the invention are contained in film-coated compressed tablets. In some embodiments, the compositions of the invention are in the form of film-coated compressed tablets.

In some embodiments, compositions of the invention are prepared by fluid bed granulation of a compound of the invention with one or more pharmaceutically acceptable carriers, vehicles or excipients. In some embodiments, compositions of the invention prepared by fluidized bed granulation have good flowability, good compressibility, rapid dissolution, good stability, and/or minimal cracking. A completely free tablet formulation can be obtained. In some embodiments, fluid bed granulation allows for the preparation of formulations with high drug loadings, such as greater than 70%, or greater than 75% of the compounds of the invention.

The compositions of the invention may be in the form of soft or hard capsules, which may be made from gelatin, methylcellulose, starch or calcium alginate. Hard gelatin capsules, also known as dry-filled capsules (DFCs), can consist of two sections, one covering the other, thus completely surrounding the active ingredient. Soft elastic capsules (SECs) are soft spherical shells, such as gelatin shells, that have been plasticized by the addition of glycerin, sorbitol or similar polyols. The soft gelatin shell can contain preservatives to inhibit microbial growth. Suitable preservatives are those described herein, including methyl and propylparaben and sorbic acid. The liquid, semi-solid and solid dosage forms provided herein can be encapsulated. Suitable liquid and semisolid dosage forms include solutions and suspensions in propylene carbonate, vegetable oils or triglycerides. Capsules containing such solutions may be prepared as described in U.S. Pat. Nos. 4,328,245, 4,409,239 and 4,410,545. Can be done. These capsules can also be coated, as known to those skilled in the art, to modify or sustain the elution of the active ingredient.

Compositions of the invention can be in liquid or semisolid dosage forms, including emulsions, solutions, suspensions, elixirs and syrups. Emulsions are two-phase systems in which one liquid is dispersed throughout the other liquid in the form of globules, which can be oil-in-water or water-in-oil. Emulsions can include pharmaceutically acceptable non-aqueous liquids or solvents, emulsifying agents and preservatives. Suspensions can contain a pharmaceutically acceptable suspending agent and preservative. The aqueous alcoholic solution may be a pharmaceutically acceptable acetal, such as a di(lower alkyl) acetal of a lower alkyl aldehyde (the term "lower" means an alkyl having between 1 and 6 carbon atoms), e.g. Acetaldehyde diethyl acetal and water-miscible solvents having one or more hydroxyl groups such as propylene glycol and ethanol can be included. The elixir can be a clear, sweetened, hydroalcoholic solution. A syrup may be a concentrated aqueous solution of a sugar, such as sucrose, and may contain a preservative. For liquid dosage forms, solutions in, for example, polyethylene glycol can be diluted with a conveniently measured amount of a pharmaceutically acceptable liquid carrier, such as water, for administration.

Compositions of the invention for oral administration may also be provided in the form of liposomes, micelles, microspheres or nanosystems. Micellar dosage forms can be prepared as described in US Pat. No. 6,350,458.

The compositions of the invention may be provided as non-effervescent or effervescent granules and powders to be reconstituted into liquid dosage forms. Pharmaceutically acceptable carriers and excipients used in non-effervescent granules or powders can include diluents, sweetening agents and wetting agents. Pharmaceutically acceptable carriers and excipients used in effervescent granules or powders can include organic acids and carbon dioxide sources.

Coloring and flavoring agents can be used in all of the above dosage forms. and flavoring and sweetening agents are particularly useful in forming chewable tablets and lozenges.

Compositions of the invention can be formulated as immediate or modified release dosage forms, including delayed release, sustained release, pulsed release, controlled release, targeted release and programmed release forms.

In some embodiments, compositions of the invention include a film coating.

Compositions of the invention may contain other active ingredients that do not confer therapeutic or prophylactic efficacy to the composition, or may contain substances that enhance or supplement the effectiveness of the composition. .

Tablet dosage forms may contain a compound of the invention in powdered crystalline or granular form, including binders, disintegrants, controlled release polymers, lubricants, diluents or colorants, as defined herein. It may further include a carrier or vehicle as described.

In some embodiments, the compositions of the invention can further include excipients such as diluents, disintegrants, wetting agents, binders, glidants, lubricants, or any combination thereof. can. In some embodiments, the tablet includes a binder. And, in some embodiments, the binder comprises microcrystalline cellulose, calcium hydrogen phosphate, sucrose, corn starch, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxymethylcellulose, or any combination thereof. In other embodiments, the tablet includes a disintegrant. In other embodiments, the disintegrant includes croscarmellose sodium, sodium starch glycolate, or any combination thereof. In other embodiments, the tablet includes a lubricant. And, in some embodiments, the lubricant comprises magnesium stearate, stearic acid, hydrogenated oil, sodium stearyl fumarate, or any combination thereof.

In some embodiments, the compositions of the invention are in the form of a tablet that includes a binder, such as any of the binders described herein.

In some embodiments, the compositions of the invention are in the form of a tablet that includes a disintegrant, such as any of the disintegrants described herein.

In some embodiments, the compositions of the invention are in the form of a tablet that includes a lubricant, such as any of the lubricants described herein.

In some embodiments, the compositions of the invention can be in modified or controlled release dosage forms. In some embodiments, compositions of the invention can include particles that exhibit a particular release profile. For example, the compositions of the invention may both contain a modified release form of a statin or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, both compressed into a single tablet. It can include a compound of the invention in a released form. Other combinations and modifications of release profiles can be realized as understood by those skilled in the art. Examples of modified release dosage forms suitable for the pharmaceutical compositions of the present invention include, but are not limited to, U.S. Pat. , No. 809, No. 3,598,123, No. 4,008,719, No. 5,674,533, No. 5,059,595, Specification No. 5,591,767, Specification No. 5,120,548, Specification No. 5,073,543, Specification No. 5,639,476, Specification No. 5,354, Specification No. 556, Specification No. 5,639,480, Specification No. 5,733,566, Specification No. 5,739,108, Specification No. 5,891,474, Specification No. 5,891,474, Specification No. Specification No. 5,922,356, Specification No. 5,972,891, Specification No. 5,980,945, Specification No. 5,993,855, Specification No. 6,045,830 Specification No. 6,087,324, Specification No. 6,113,943, Specification No. 6,197,350, Specification No. 6,248,363, Specification No. No. 6,264,970, No. 6,267,981, No. 6,376,461, No. 6,419,961, No. 6,589,548 Specification No. 6,613,358, No. 6,699,500.

In some embodiments, the compositions of the invention are matrix controlled release dosage forms. In some embodiments, the release profiles of the compounds of the invention and other pharmaceutically active agents are the same or different. Suitable matrix controlled release dosage forms are described, for example, in Takada et al in "Encyclopedia of Controlled Drug Delivery," Vol. 2, Mathiowitz ed., Wiley, 1999.

In some embodiments, matrix controlled release forms include erodible matrices that include water-swellable, water-erodible, or water-soluble polymers, including synthetic polymers and natural polymers and derivatives, such as polysaccharides and proteins.

In some embodiments, the erodible matrix of the matrix controlled release form is chitin, chitosan, dextran or pullulan; gum agar, gum arabic, gum karaya, locust bean gum, gum tragacanth, carrageenan, gum gatch, guar gum, xanthan gum or screoglucan. starch such as dextrin or maltodextrin; hydrophilic colloid such as pectin; phospholipid such as lecithin; alginate; propylene glycol alginate; gelatin; collagen; ethyl cellulose (EC), methyl ethyl cellulose (MEC), carboxymethyl cellulose (CMC), carboxy Methyl ethyl cellulose (carrrboxymethyl ethyl cellulose) (CMEC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), cellulose acetate (CA), cellulose propionate (CP), cellulose butyrate (CB), cellulose acetate butyrate (CAB), Cellulosics such as cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), hydroxypropylmethylcellulose (HPMC), HPMCP, HPMCAS, hydroxypropylmethylcellulose acetate trimellitate (HPMCAT) or ethylhydroxyethylcellulose (EHEC); polyvinylpyrrolidone polyvinyl alcohol; polyvinyl acetate; glycerol fatty acid ester; polyacrylamide; polyacrylic acid; copolymer with ethacrylic acid or methacrylic acid (EUDRAGIT®, Rohm America, Inc., Piscataway, NJ); poly(2-hydroxy polylactide; copolymer of L-glutamic acid and ethyl-L-glutamic acid; degradable lactic acid-glycolic acid copolymer; poly-D-(-)-3-hydroxybutyric acid; or butyl methacrylate, methyl methacrylate, ethyl methacrylate , ethyl acrylate, (2-dimethylaminoethyl) methacrylate or other acrylic acid derivatives such as homopolymers and copolymers of (trimethylaminoethyl) methacrylate; or any combination thereof.

In other embodiments, the compositions of the invention are in a matrix controlled modified release form that includes a non-erodible matrix. In some embodiments, the statin, a compound of the invention, is dissolved or dispersed in an inert matrix and, once administered, is released primarily by diffusion through the inert matrix. In some embodiments, the non-erodible matrix of the matrix controlled release form is polyethylene, polypropylene, polyisoprene, polyisobutylene, polybutadiene, polymethyl methacrylate, polybutyl methacrylate, chlorinated polyethylene, polyvinyl chloride, methyl acrylate. Methyl methacrylate copolymer, ethylene-vinyl acetate copolymer, ethylene/propylene copolymer, ethylene/ethyl acrylate copolymer, vinyl chloride copolymer with vinyl acetate, vinylidene chloride, ethylene or propylene, ionomer polyethylene terephthalate, butyl rubber epichlorohydrin rubber, ethylene/ Insoluble materials such as vinyl alcohol copolymers, ethylene/vinyl acetate/vinyl alcohol terpolymers, ethylene/vinyloxyethanol copolymers, polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalate, natural rubber, silicone rubber, polydimethylsiloxane, silicone carbonate copolymers, etc. polymers or hydrophilic polymers such as ethylcellulose, cellulose acetate, crospovidone or crosslinked partially hydrolyzed polyvinyl acetate; fatty compounds such as carnauba wax, microcrystalline wax or triglycerides; or any combination thereof.

Compositions of the invention in modified release dosage forms can be prepared by methods known to those skilled in the art, including direct compression, dry or wet granulation followed by compression, melt granulation followed by compression.

In some embodiments, the compositions of the invention include a tablet-in-capsule system, which can be a multifunctional, multi-unit system that includes versatile mini-tablets in hard gelatin capsules. be. The minitablets can be rapid release, sustained release, pulsed, delayed onset sustained release minitablets, or any combination thereof. In some embodiments, each combination of minitablets or combinations of minitablets and minibeads containing a plurality of active pharmaceutical agents is used in a multi-release pulsed drug delivery system (DDS), a site-specific DDS, a slow-release - Can have specific time differences: rapid DDS, rapid/slow DDS and zero-order DDS.

In some embodiments, the compositions of the invention are in an osmotically controlled release dosage form.

In some embodiments, the osmotically controlled release device comprises a one-chamber system, a two-chamber system, asymmetric membrane technology (AMT), an extruded core system (ECS), or any combination thereof. In some embodiments, such devices are semipermeable with at least two components: (a) a core containing the active pharmaceutical agent, and (b) at least one delivery port enclosing the core. A membrane is provided. The semipermeable membrane controls the flow of water from the aqueous environment of use toward the core to cause drug release by extrusion from the delivery port.

In some embodiments, the core of the osmotic device optionally includes an osmotic agent that creates a motive force to transport water from the environment of use to the core of the device. One class of osmotic agents useful in the compositions of the invention include, but is not limited to, hydrophilic vinyl and acrylic polymers, polysaccharides such as calcium alginate, polyethylene oxide (PEO), polyethylene glycol (PEG), polypropylene Glycol (PPG), poly(2-hydroxyethyl methacrylate), poly(acrylic) acid, poly(methacrylic) acid, polyvinylpyrrolidone (PVP), crosslinked PVP, polyvinyl alcohol (PVA), PVA/PVP copolymer, methyl methacrylate and PVA/PVP copolymers with hydrophobic monomers such as vinyl acetate, hydrophilic polyurethanes containing large PEO blocks, croscarmellose sodium, carrageenan, hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC) ), carboxymethyl cellulose (CMC) and carboxyethyl cellulose (CEC), sodium alginate, polycarbophil, gelatin, xanthan gum and sodium starch glycolate, also referred to as "osmopolymers" or "hydrogels" , including water-swellable hydrophilic polymers.

Another class of osmotic agents useful in the compositions of the invention includes osmogens, which can absorb water and affect the osmotic pressure gradient across the barrier around the coating. can. Suitable osmogens include, but are not limited to, magnesium sulfate, magnesium chloride, calcium chloride, sodium chloride, lithium chloride, potassium sulfate, potassium phosphate, sodium carbonate, sodium sulfite, lithium sulfate, potassium chloride, and sodium sulfate. Inorganic salts; sugars such as dextrose, fructose, glucose, inositol, lactose, maltose, mannitol, raffinose, sorbitol, sucrose, trehalose and xylitol; ascorbic acid, benzoic acid, fumaric acid, citric acid, maleic acid, sebacic acid, sorbic acid , adipic acid, edetic acid, glutamic acid, p-toluenesulfonic acid, succinic acid and tartaric acid; urea; and mixtures thereof.

Osmotic agents of different dissolution rates can be used to influence how quickly a compound of the invention dissolves after administration. For example, amorphous sugars such as Mannogeme EZ (SPI Pharma, Lewes, DE) may be included to achieve faster delivery and increase prophylactic efficacy or Therapeutic efficacy can occur rapidly and residual amounts can be released gradually and sustainably to maintain a desired level of therapeutic or prophylactic effect over time. In some embodiments, the compound of the invention is released from the composition of the invention at a rate that replaces the amount of the compound of the invention that is metabolized or excreted by the subject.

The core can also include a wide variety of other excipients and carriers as described herein to enhance the performance of the dosage form or promote stability or facilitate processing.

Materials useful in the formation of semipermeable membranes include various grades of acrylics, vinyls, etc. that are water permeable and water insoluble at physiologically relevant pH, or that are susceptible to becoming insoluble through chemical modification such as cross-linking. Includes ethers, polyamides, polyesters and cellulose derivatives. Examples of suitable polymers useful in forming coatings include plasticized, unplasticized and reinforced cellulose acetate (CA), cellulose diacetate, cellulose triacetate, CA propionate, cellulose nitrate, cellulose acetate butyrate (CAB). , CA ethyl carbamate, CAP, CA methyl carbamate, CA succinate, cellulose acetate trimellitate (CAT), CA dimethylaminoacetate, CA ethyl carbonate, CA chloroacetate, ethyl oxalate CA, methyl sulfonate Ca, butyl sulfonate CA, p-toluenesulfonic acid CA, agar acetate, amylose triacetate, beta glucan acetate, beta glucan triacetate, acetaldehyde dimethyl acetate, locust bean gum triacetate, ethylene hydroxide-vinyl acetate, EC, PEG, PPG, PEG /PPG copolymers, PVP, HEC, HPC, CMC, CMEC, HPMC, HPMCP, HPMCAS, HPMCAT, poly(acrylic) acids and esters, and poly-(methacrylic) acids and esters and copolymers thereof, starch, dextran, dextrin, chitosan , collagen, gelatin, polyalkenes, polyethers, polysulfones, polyethersulfones, polystyrenes, polyvinyl halides, polyvinyl esters and ethers, natural waxes, and synthetic waxes.

The semipermeable membrane can also be a hydrophobic microporous membrane, as disclosed in U.S. Pat. No. 5,798,119, in which the pores are substantially impervious to gas. filled and not wetted by aqueous media, but permeable to water vapor. Such hydrophobic but water vapor permeable membranes are typically made of polyalkenes, polyethylene, polypropylene, polytetrafluoroethylene, polyacrylic acid derivatives, polyethers, polysulfones, polyethersulfones, polystyrene, polyvinyl halides, polyvinylidene fluoride, Consists of hydrophobic polymers such as polyvinyl esters and ethers, natural waxes and synthetic waxes.

Delivery ports on the semipermeable membrane can be formed after coating by mechanical or laser drilling. Delivery ports may also be formed in situ by erosion of a plug of water-soluble material or by rupture of a thinner portion of the membrane over an indentation in the core. Additionally, the delivery port may be used during the coating process, as is the case with asymmetric membrane coatings of the type disclosed in U.S. Pat. No. 5,612,059 and U.S. Pat. can be formed.

The total amount of compounds of the invention released and the rate of release can be substantially controlled by the thickness and porosity of the semipermeable membrane, the composition of the core, and the number, size, and location of the delivery ports.

In some embodiments, the pharmaceutical composition in an osmotically controlled release dosage form further comprises additional conventional excipients as described herein to facilitate performance or processing of the formulation. be able to.

Osmotically controlled release dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art (Remington: The Science and Practice of Pharmacy, supra; Santus and Baker, J. Controlled Release 1995, 35 , 1-21; Verma et al., Drug Development and Industrial Pharmacy 2000, 26, 695-708; Verma et al., J. Controlled Release 2002, 79, 7-27).

In some embodiments, the pharmaceutical compositions provided herein utilize asymmetric membrane technology (AMT) comprising an asymmetric osmotic membrane coating a core containing the active ingredient and other pharmaceutically acceptable excipients. ) formulated as a controlled release dosage form. See US Pat. No. 5,612,059 and WO 2002/17918. AMT controlled release dosage forms can be prepared according to conventional methods and techniques known to those skilled in the art, including direct compression, dry granulation, wet granulation and dip coating methods.

In some embodiments, the pharmaceutical compositions provided herein comprise an ESC comprising an osmotic membrane coating a core comprising a compound of the invention, hydroxylethylcellulose, and other pharmaceutically acceptable excipients. Formulated as a controlled release dosage form.

In some embodiments, the compositions of the invention comprise a plurality of particles, granules or pellets, microparticles, beads, ranging in diameter from about 10 μm to about 3 mm, from about 50 μm to about 2.5 mm, or from about 100 μm to 1 mm. Modified release dosage forms manufactured as multiparticulate controlled release dosage forms, including microcapsules and microtablets.

Multiparticulate controlled release dosage forms can provide extended release dosage forms with improved bioavailability. Suitable carriers for sustaining the rate of release of the compounds of the invention include, but are not limited to, ethylcellulose, HPMC, HPMC-phthalate, colloidal silicon dioxide, and Eudragit-RSPM.

Compositions of the invention in pellet form can contain 50-80% (w/w) drug and 20-50% (w/w) microcrystalline cellulose or other polymer. Suitable polymers include, but are not limited to, microcrystalline waxes, pregelatinized starches, and maltose dextrins.

Beads can be prepared in capsule and tablet dosage forms. Beads in tablet dosage forms can demonstrate slower dissolution profiles than microparticles in capsule dosage forms. Microparticle fillers suitable for the compositions and therapeutic or prophylactic methods of the invention include, but are not limited to, sorbitan monooleate (Span 80), HPMC, or any combination thereof. Dispersions suitable for controlled release latex include, for example, ethyl-acrylate and methyl-acrylate.

In some embodiments, the compositions of the invention are present in the form or in microcapsules and/or microtablets. In some embodiments, the microcapsules include sustained release polymeric microcapsules containing a statin and a compound of the invention with varying solubility characteristics. Sustained release polymer microcapsules can be prepared using colloidal polymer dispersions in an aqueous environment. In other embodiments, microcapsules suitable for the compositions and methods provided herein can be prepared using conventional microencapsulation techniques (Bodmeier & Wang, 1993).

Such multiparticulates can be made by methods known to those skilled in the art, including by wet and dry granulation, extrusion/spheronization, roller compaction, melt congealing, and spray coating of seed cores. See, eg, Multiparticulate Oral Drug Delivery; Marcel Dekker: 1994; and Pharmaceutical Pelletization Technology; Marcel Dekker: 1989. Excipients for such techniques are commercially available and listed in the United States Pharmacopeia.

Other excipients described herein can be blended with the compositions of the invention to aid in processing and forming multiparticulates. The resulting particles can themselves constitute a multiparticulate dosage form or can be coated with various film-forming materials such as enteric, water-swellable or water-soluble polymers. Multiparticulates can be further processed as capsules or tablets.

In other embodiments, the compositions of the invention are in a dosage form having an immediate release component and at least one delayed release component, spaced apart in time from 0.1 hours to 24 hours. It is possible to provide discontinuous release of the compound in the form of at least two consecutive pulses.

In some embodiments, compositions of the invention contain an amount of a compound of the invention from about 1 mg to about 1000 mg, or any range between these values. In some embodiments, compositions of the invention contain an amount of a compound of the invention from about 1 mg to about 500 mg, or any range between these values. In some embodiments, compositions of the invention contain an amount of a compound of the invention from about 1 mg to about 400 mg, or any range between these values.

In other embodiments, the compositions of the invention contain a compound of the invention in an amount that provides the equivalent number of moles of the compound of the invention from about 1 mg to about 1000 mg or any amount between these values. include. In other embodiments, the compositions of the invention contain a compound of the invention in an amount that provides the equivalent number of moles of the compound of the invention from about 1 mg to about 500 mg or any amount ranging between these values. include. In other embodiments, the compositions of the invention contain a compound of the invention in an amount that provides the equivalent number of moles of the compound of the invention from about 1 mg to about 400 mg or any amount between these values. include.

In some embodiments, compositions of the invention contain a compound of the invention in an amount from about 10% to about 99% by weight of the total weight of the composition of the invention.

5.4. Method of the present invention The present invention is directed to liver disorders, lipid metabolism abnormalities, dyslipoproteinemia, renal diseases, disorders of glucose metabolism, disorders of lipid metabolism, disorders of carbohydrate metabolism, cardiovascular diseases, vascular diseases, metabolic syndrome, Complications associated with metabolic syndrome, PPAR-related disorders, sepsis, thrombotic disorders, obesity, diabetic nephropathy, diabetic retinopathy, atherosclerosis, pancreatitis, cerebrovascular disease, angiogenesis-related disorders, hypertension, A method for treating or preventing inflammation, inflammatory diseases, neurodegenerative diseases, autoimmune diseases, oncological diseases, muscle atrophy, cholestasis, mitochondrial dysfunction, eye diseases, lysosomal storage diseases, or erectile dysfunction, , a method comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. The present invention is a method of treating or preventing kidney disease (e.g., acute kidney injury) comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. , provides a method.

In some embodiments, the invention provides a method of treating or preventing liver damage comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. , provides a method. In some embodiments, liver damage includes pathological destruction, inflammation, degeneration, apoptosis, or proliferation of liver cells. In some embodiments, the liver disorder is liver fibrosis, fatty liver disease, nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH).

In some embodiments, the invention provides a method for detecting abnormally high concentrations of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, gamma-glutamyl transferase (ALP) in the plasma or serum of a subject. GGT), L-lactate dehydrogenase (LD), prothrombin time (PT), creatinine or total protein, comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. A method is provided, comprising the step of administering. In some embodiments, the present invention provides a method for improving abnormally low concentrations of albumin or total protein in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of the present invention. A method is provided comprising administering a compound or composition of the invention.

An "abnormally high concentration" of ALT in a subject's plasma or serum is greater than 56 units/liter. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of ALT in the subject's plasma or serum ranges from about 7 units/liter to about 56 units/liter.

An "abnormally high concentration" of AST in a subject's plasma or serum is greater than 48 units/liter. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of AST in the subject's plasma or serum ranges from about 8 units/liter to about 48 units/liter.

An "abnormally high concentration" of ALP in a subject's plasma or serum is greater than 129 units/liter. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of ALP in the subject's plasma or serum ranges from about 40 units/liter to about 129 units/liter.

An "abnormally low concentration" of albumin in a subject's plasma or serum is less than 3.5 g/dL. In some embodiments, the increase is to normal concentrations. In some embodiments, the normal concentration of albumin in the subject's plasma or serum ranges from about 3.5 g/dL to about 5.0 g/dL.

An "abnormally high concentration" of bilirubin in a subject's plasma or serum is greater than 1.2 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of bilirubin in the subject's plasma or serum ranges from about 0.1 mg/dL to about 1.2 mg/dL.

An "abnormally high concentration" of GGT in a subject's plasma or serum is greater than 61 units/liter. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of GGT in the subject's plasma or serum ranges from about 8 units/liter to about 61 units/liter.

An "abnormally high concentration" of LD in a subject's plasma or serum is greater than 222 units/liter. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of LD in the subject's plasma or serum ranges from about 122 units/liter to about 222 units/liter.

An "abnormally high concentration" of PT in a subject's plasma or serum is longer than 12.5 seconds. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of PT in the subject's plasma or serum ranges from about 9.4 seconds to about 12.5 seconds.

An "abnormally high concentration" of creatinine in a subject's plasma or serum is greater than 1.5 mg/dL, corresponding to a glomerular filtration rate (GFR) of approximately 30 mL/min, and indicative of renal failure. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of creatinine in the subject's plasma or serum ranges from about 0.84 mg/dL to about 1.21 mg/dL (about 74.3 μmol/L to about 107 μmol/L). .

An "abnormally high concentration" of total protein in a subject's plasma or serum is greater than 7.9 g/dL. An "abnormally low concentration" of total protein in a subject's plasma or serum is less than 6.3 g/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the increase is to normal concentrations. In some embodiments, the normal concentration of total protein in the subject's plasma or serum ranges from about 6.3 g/dL to about 7.9 g/dL.

In some embodiments, the invention provides a method of treating or preventing NAFLD or NASH comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provides a method, including.

In some embodiments, the invention provides a method of treating or preventing dyslipidemia, which comprises administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the dyslipidemia is hyperlipidemia or an abnormally low concentration of high density lipoprotein cholesterol (HDL-C) in the subject's plasma or serum. The term "dyslipidemia" refers to disorders resulting in or manifested by abnormal levels of circulating lipids.

In some embodiments, the invention provides plasma or serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, or free triglycerides at normal or recommended concentrations. Or provide a method to restore the ratio. Accordingly, a compound of the invention or a composition of the invention may be administered to a patient to the extent that the level of lipids in plasma or serum is abnormally high until restored to normal levels. Normal levels of lipids are well known to those skilled in the art. For example, normal blood levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, free triglycerides, and other parameters related to lipid metabolism are described by the American Heart Association, The It can be found on the website of the National Lipid Association and the website of the National Cholesterol Education Program of the National Heart, Lung and Blood Institute. I can. In some embodiments, the recommended concentration of HDL-C in plasma or serum is greater than 35 mg/dl. In some embodiments, the recommended concentration of LDL-C in plasma or serum is less than 100 mg/dl. In some embodiments, the recommended LDL-C:HDL-C ratio in plasma or serum is less than 5:1, and in some embodiments less than 3.5:1. In some embodiments, the recommended concentration of free triglycerides in plasma or serum is less than 200 mg/dl.

In some embodiments, the invention provides a method of treating or preventing hyperlipidemia, the method comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method including. In some embodiments, the hyperlipidemia is hypercholesterolemia, familial hypercholesterolemia, hypertriglyceridemia, or familial combined hyperlipidemia. In some embodiments, hyperlipidemia is an abnormally reduced or deficient lipoprotein lipase level or activity in the subject's plasma or serum, or ketone bodies, lipoprotein (a) cholesterol ( It is characterized by abnormally high concentrations of Lp(a)-C), low density lipoprotein (LDL), very low density lipoprotein cholesterol (VLDL-C) or non-esterified fatty acids (NEFA). In some embodiments, a reduction or deficiency in lipoprotein lipase levels or activity is the result of a lipoprotein lipase mutation. In some embodiments, a reduction or deficiency in lipoprotein lipase levels or activity is the result of a mutation in the gene encoding lipoprotein lipase.

Non-limiting examples of ketone bodies include acetoacetate, beta-hydroxybutyrate and acetone. An "abnormally high concentration" of ketone bodies in a subject's plasma or serum is greater than or equal to 1 mg/dL (<0.1 mmol/L). In some embodiments, the invention provides a method of reducing an abnormally high concentration of ketone bodies in the plasma or serum of a subject, wherein the concentration is 1 mg/dL or more. In some embodiments, the reduction is to normal levels. In some embodiments, normal levels are less than 1 mg/dL (<0.1 mmol/L). See Devkota, B. P. et al. Medscape emedicine, updated October 30, 2015.

An "abnormally high concentration" of VLDL-C in a subject's plasma or serum is greater than 30 mg/dL (1.7 mmol/L). In some embodiments, the invention provides a method of reducing VLDL-C concentration in plasma or serum of a subject, wherein the VLDL-C concentration is greater than 30 mg/dL. In some embodiments, the reduction is to normal levels. In some embodiments, normal levels range from 2 mg/dL to 30 mg/dL (0.1 to 1.7 mmol/L).

An "abnormally high concentration" of NEFA in a subject's plasma or serum in a non-fasting state is 0.9 mM or more. An "abnormally high concentration" of NEFA in a subject's plasma or serum in the fasting state is greater than 1.8 mM in the fasting state. An "abnormally high concentration" of NEFA in a subject's plasma or serum after 15 hours of fasting is greater than 1.1 nM. An "abnormally high concentration" of NEFA in a subject's plasma or serum after 20 hours of fasting is greater than 1.3 mM. An "abnormally high concentration" of NEFA in a subject's plasma or serum after 15 hours of fasting is greater than 1.1 nM. An "abnormally high concentration" of NEFA in a subject's plasma or serum during a 24-hour fasting period is greater than 1.8 mM. In some embodiments, the invention provides a method of reducing NEFA concentration in plasma or serum of a subject, the NEFA concentration being greater than 0.9 mM, and in some embodiments greater than 1.1 mM. , in some embodiments higher than 1.5mM, and in some embodiments higher than 1.8mM. In some embodiments, the reduction is to normal levels. In some embodiments, the normal level is 1.8mM or less, in some embodiments 1.5mM or less, in some embodiments 1.1mM or less, and in some embodiments In terms of form, it is 0.9mM or less. See Horowitz, G. L. et al. Medscape emedicine, updated July 25, 2019.

In some embodiments, the invention provides a method of treating or preventing dyslipoproteinemia, comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provides a method comprising steps. In some embodiments, dyslipoproteinemia is characterized by abnormally high concentrations of LDL, apolipoprotein (a), or VLDL in the subject's plasma or serum, or abnormally low concentrations of LDL, apolipoprotein (a), or VLDL in the subject's plasma or serum. It is characterized by density lipoprotein (HDL) or lipoprotein lipase. In some embodiments, abnormally low levels of lipoprotein lipase are associated with lipoprotein lipase mutations, hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, and lipoprotein abnormalities associated with Alzheimer's disease. Associated with protein abnormalities or familial combined hyperlipidemia. The term "dyslipoproteinemia" refers to a disorder resulting in or manifested by abnormal concentrations of circulating lipoproteins in the plasma or serum of a subject. A compound of the invention or a composition of the invention may be administered to a subject to restore normal concentrations of lipoproteins to the extent that the concentration of lipoproteins in plasma or serum is too high. Conversely, a compound of the invention or a composition of the invention may be administered to a subject to the extent that the concentration of lipoproteins in plasma or serum is too low to restore normal concentrations. Normal concentrations of lipoproteins are reported in medical literature known to those skilled in the art.

In some embodiments, the invention provides a method of treating or preventing renal disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, the renal disease is a glomerular disease, a tubular disease, a tubulointerstitial disease, an acute or rapidly progressive renal failure, a chronic renal failure, a renal stone, or a tumor. In some embodiments, the renal disease is hypertension, nephrosclerosis, microangiopathic hemolytic anemia, atheroembolic renal disease, diffuse cortical necrosis, or renal embolism.

In some embodiments, the glomerular disease is acute glomerulonephritis, chronic glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, focal proliferative glomerulonephritis, glomerular lesions associated with systemic disease, Pasture syndrome, multiple myeloma, diabetes, neoplasia, sickle cell disease or chronic inflammatory disease. In some embodiments, the glomerular pathology associated with systemic disease is systemic lupus erythematosus.

In some embodiments, the tubular disease is acute tubular necrosis, acute renal failure, polycystic kidney disease, medullary cavernous kidney, medullary cystic disease, renal diabetes, or renal tubular acidosis.

In some embodiments, the tubulointerstitial disease is pyelonephritis, drug- or toxin-induced tubulointerstitial nephritis, hypercalcic nephropathy, or hypokalemic nephropathy.

In some embodiments, the tumor is renal cell carcinoma or nephroblastoma.

In some embodiments, the renal disease is hypertension. In some embodiments, the hypertension is essential hypertension, hyperpiesa, hyperpiersis, malignant hypertension, secondary hypertension or white coat hypertension.

In some embodiments, the renal disease is renal disease.

In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method including. The term "disorder of glucose metabolism" refers to a disorder resulting in or manifested by abnormalities in glucose accumulation and/or utilization. A compound of the invention or a composition of the invention may be administered to a subject to the extent that indicators of glucose metabolism (i.e., insulin, glucose or glycated hemoglobin in the subject's plasma or serum) are too high to restore them to normal levels. . Normal indicators of glucose metabolism are reported in medical literature known to those skilled in the art. See US Pat. No. 7,709,682.

In some embodiments, the invention provides a method of lowering abnormally high concentrations of glucose in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. An "abnormally high concentration" of glucose in a subject's plasma or serum during a fasting state (10-16 hours without eating) is greater than 5.6 mmol/L (100 mg/dL). In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of glucose is less than 5.6 mmol/L in the fasting state. In some embodiments, a fasting plasma or serum concentration of glucose in the range of 5.6 mmol/L to 6 mmol/L (100-109 mg/dL) may be indicative of prediabetes. In some embodiments, a fasting plasma or serum concentration of glucose in the range of 6.1 mmol/L to 6.9 mmol/L (110 to 125 mg/dL) may be indicative of diabetes. be. In some embodiments, a fasting plasma or serum concentration of glucose greater than or equal to 7 mmol/L (126 mg/dL) is indicative of diabetes.

In some embodiments, the abnormally high concentration of glucose in the subject's plasma or serum is measured with a glucose tolerance test (GTT).

An "abnormally high concentration" of glucose in a subject's plasma or serum at 1 hour GTT is greater than 10 mmol/L (180 mg/dL). In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration at 1 hour GTT is less than 10 mmol/L (180 mg/dL).

An "abnormally high concentration" of glucose in a subject's plasma or serum at 2 hours GTT for a 75 g intake is greater than 7.8 mmol/L (140 mg/dL), which is associated with hyperglycemia. Show that something is true. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration at 2 hours GTT for a 75 g intake is less than 7.8 mmol/L (140 mg/dL). In some embodiments, the glucose concentration in the plasma or serum of the subject is between 7.8 mmol/L (140 mg/dL) and 11.1 mmol/L (200 mg/dL) at 2 hours GTT for a 75 g ingestion. indicates impaired glucose tolerance. In some embodiments, a glucose concentration greater than 11.1 mmol/L at 2 hours GTT for a 75 g intake is indicative of diabetes.

In some embodiments, the present invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the concentration of glucose in the subject's plasma or serum is 7.8 mmol/L at 2 hours GTT. 140 mg/dL). In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the concentration of glucose in the subject's plasma or serum is 7.8 mmol/L at 2 hours GTT. (140 mg/dL) to 11.1 mmol/L (200 mg/dL). In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the concentration of glucose in the subject's plasma or serum is 11.1 mmol/L at 2 hours GTT. (200 mg/dL).

In some embodiments, the invention provides a method of reducing abnormally high levels of HbA _1c in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising administering a composition of the invention. An "abnormally high level" of hemoglobin A1c ( _HbA1c ) in a subject's plasma or serum is 6.5% or more (expressed in %NGSP). In some embodiments, the reduction is to normal levels. In some embodiments, normal levels of HbA _1c range from about 4% to about 5.9%. In some embodiments, the invention provides a method of reducing HbA _1c levels in plasma or serum of a subject, wherein the HbA _1c level is greater than 7%, greater than 8%, or greater than 9%. provide a method. See Horowitz, GL et al. Medscape emedicine, updated July 25, 2019.

In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, the subject's HbA _1c level in the subject's plasma or serum being 6.5% or higher, and the subject's has a fasting glucose concentration of 126 mg/dL or more (≧7.0 mmol/L). See Selvin, E. et al. Ann Intern Med. Published online June 18, 2018.

In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject has an HbA _1c of 6.5% or greater. In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject has an HbA _1c of 6.5% or greater in the subject's plasma or serum. , and the fasting glucose concentration is 126 mg/dL (7.0 mmol/L) or more.

In some embodiments, the present invention provides methods for reducing abnormally high concentrations in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the present invention or a composition of the present invention. Provided are methods for lowering glucose in a subject, the subject being pregnant. An "abnormally high concentration" of glucose in the fasting plasma or serum of a pregnant subject is greater than 5.3 mmol/L (95 mg/dL).

In some embodiments, the invention provides a method for lowering abnormally high concentrations of glucose in the plasma or serum of a subject, comprising: (i) completing a two-step gestational diabetes test; and (ii) administering an effective amount of a compound of the invention or a composition of the invention. In a two-step gestational diabetes test, an "abnormally high concentration" of glucose in a subject's plasma or serum one hour after drinking the glucose solution is greater than 10 mmol/L (180 mg/dL). In the two-step procedure, the first step is a 50 g glucose dose. If blood glucose levels result in higher than 7.8 mmol/L (140 mg/dL), then a glucose dose of 100 g. In a two-step gestational diabetes test, an "abnormally high concentration" of glucose in a subject's plasma or serum two hours after drinking the glucose solution is greater than 8.6 mmol/L (155 mg/dL). be. In a two-step gestational diabetes test, an "abnormally high concentration" of glucose in a subject's plasma or serum three hours after drinking the glucose solution is greater than 7.8 mmol/L (140 mg/dL). be.

In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject has impaired glucose tolerance. In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject has diabetes. In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject is confirmed to have undiagnosed diabetes. In some embodiments, the invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject has gestational diabetes.

In some embodiments, the invention provides a method of lowering abnormally high concentrations of insulin in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. An "abnormally high concentration" of insulin in a subject's plasma or serum during fasting is greater than 25 mIU/L (>174 pmol/L). In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of insulin in the subject's plasma or serum during fasting is less than 25 mIU/L (<174 pmol/L). See Buppajarntham, S. et al. Medscape, updated January 2, 2019.

In some embodiments, the invention provides a method of lowering abnormally high concentrations of insulin in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention.

In some embodiments, the method further comprises administering glucose to the subject. In some embodiments, the method does not include administering glucose to the subject. In some embodiments, the subject is in a fasted state.

In some embodiments, the subject has an abnormal concentration of insulin or blood sugar in the subject's plasma 30 minutes after administering glucose. An "abnormally high concentration" of insulin in a subject's plasma or serum 30 minutes after administering glucose is greater than 230 mIU/L (>1597 pmol/L). In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of insulin in the subject's plasma or serum 30 minutes after administering glucose is in the range of about 30 mIU/L to about 230 mIU/L (208-1597 pmol/L). . See Buppajarntham, 2019.

In some embodiments, the subject has an abnormal insulin concentration in the subject's plasma or serum one hour after administering glucose. An "abnormally high concentration" of insulin in a subject's plasma or serum one hour after administration of glucose is greater than 276 mIU/L (>1917 pmol/L). In some embodiments, the invention provides a method of lowering abnormally high concentrations of insulin in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. In some embodiments, the reduction is to normal concentrations. In some embodiments, one hour after administering glucose, the normal concentration of insulin in the subject's plasma or serum ranges from about 18 mIU/L to about 276 mIU/L (125-1917 pmol/L). See Buppajarntham, 2019.

In some embodiments, the subject has abnormal concentrations of insulin or blood sugar in the subject's plasma 2 hours after administering glucose. An "abnormally high concentration" of insulin in a subject's plasma or serum two hours after administration of glucose is greater than 166 mIU/L (>1153 pmol/L). In some embodiments, the invention provides a method of lowering abnormally high concentrations of insulin in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. In some embodiments, the normal concentration of insulin in the subject's plasma or serum 2 hours after administering glucose is in the range of about 16 mIU/L to about 166 mIU/L (111-1153 pmol/L). . See Buppajarntham, 2019.

In some embodiments, the subject has abnormal concentrations of insulin or blood sugar in the subject's plasma 3 hours after administering glucose. An "abnormally high concentration" of insulin in a subject's plasma or serum three hours after administration of glucose is greater than 25 mIU/L (>174 pmol/L). In some embodiments, the invention provides a method of lowering abnormally high concentrations of insulin in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. In some embodiments, the normal concentration of insulin in the subject's plasma or serum at 3 hours or more after administering glucose is less than 25 mIU/L (<174 pmol/L). See Buppajarntham, 2019.

In some embodiments, the present invention provides a method of treating or preventing a disorder of glucose metabolism in a subject, wherein the subject is in a fasting state or 3 hours after administration of glucose, , having an insulin concentration higher than 25 mIU/L. See Buppajarntham, 2019.

In some embodiments, the disorder of glucose metabolism is glucose intolerance; insulin resistance; insulin resistance-associated breast, colon, or prostate cancer; diabetes; pancreatitis; hypertension; polycystic ovarian disease; or an abnormally high concentration of blood insulin or glucose in the serum. In some embodiments, the diabetes is non-insulin dependent diabetes mellitus (NIDDM), insulin dependent diabetes mellitus (IDDM), gestational diabetes mellitus (GDM) or young onset adult diabetes mellitus (MODY).

In some embodiments, the invention provides a method of treating or preventing metabolic syndrome (Syndrome X) comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. A method is provided that includes the steps of: In some embodiments, the invention provides a method of treating or preventing symptoms of metabolic syndrome (Syndrome X), comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. A method is provided comprising the step of administering. In some embodiments, the condition is glucose intolerance, hypertension, dyslipidemia, or dyslipoproteinemia.

In some embodiments, the invention provides a method of treating or preventing vascular or cardiovascular disease, comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. A method is provided that includes the steps of: The term "cardiovascular disease" refers to diseases of the heart or circulatory system. In some embodiments, the vascular or cardiovascular disease is peripheral vascular disease, coronary heart disease, stroke, restenosis, atherosclerosis, ischemia, endothelial dysfunction, ischemia-reperfusion injury, myocardial infarction, or It was a cerebral infarction.

In some embodiments, the invention provides a method of treating or preventing a PPAR-related disorder comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the PPAR-associated disorder is rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, breast cancer, colon cancer, or prostate cancer. In some embodiments, the PPAR-related disorder is a vascular disease, a muscle disease, a demyelinating disease, a muscle structural disorder, a neural activation disorder, a muscle wasting disorder, a muscle mass disorder, a mitochondrial disease, a mitochondrial dysfunction, a beta oxidation disease. or metabolic disease. In some embodiments, the PPAR-related disorder comprises an abnormally low concentration of HDL, an abnormally low concentration of apolipoprotein A-I (apoA-I), an abnormally high concentration of VLDL in the plasma or serum of the subject. -C, abnormally high levels of low-density lipoprotein cholesterol (LDL-C), abnormally high levels of triglycerides, abnormally high levels of apolipoprotein B (apoB), abnormally high levels of apolipoprotein C-III ( The abnormally decreased ratio of hepatic lipase to apoC-III) or lipoprotein lipase activity after heparin administration. In some embodiments, the PPAR-related disorder is an abnormally high concentration of HDL or an abnormally low concentration of ApoA-I in the lymph or cerebrospinal fluid of the subject.

In some embodiments, the PPAR-related disorder is an abnormally low concentration of lipoprotein lipase activity in the subject's post-heparin plasma (the subject's plasma after intravenous injection of heparin). In some embodiments, the invention provides a method for improving abnormally low levels of lipoprotein lipase activity in plasma after administration of heparin, comprising administering to a subject in need thereof an effective amount of a compound of the invention. Alternatively, a method is provided comprising the step of administering a composition of the invention. An "abnormally low concentration" of lipoprotein lipase activity in plasma after heparin administration is less than 30 U/L. In some embodiments, the increase is to normal concentrations. In some embodiments, normal concentrations range from about 30 U/L to about 153 U/L (see Nakajima et al. Clin Chim Acta. 2018 Dec;487:54-59).

In some embodiments, the invention provides a method of treating or preventing a PPAR-related disorder in a subject, wherein the subject has a lipoprotein lipase activity in plasma after heparin administration of less than 30 U/L.

In some embodiments, the subject is a male subject. An "abnormally high concentration" of HDL in a male subject is greater than 75 mg/dL.

In some embodiments, the subject is a female subject. An "abnormally high concentration" of HDL in a female subject is greater than 90 mg/dL.

In some embodiments, the invention provides a method of reducing abnormally high concentrations of HDL in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising the step of administering a composition of the invention. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration for male subjects is less than 75 mg/dL. In some embodiments, the normal concentration for female subjects is less than 90 mg/dL. In some embodiments, the invention provides a method of treating or preventing a PPAR-related disorder in a male subject, wherein the subject has an HDL concentration greater than 75 mg/dL in the subject's plasma or serum. provide. In some embodiments, the invention provides a method of treating or preventing a PPAR-related disorder in a female subject, wherein the subject has an HDL concentration greater than 90 mg/dL in the subject's plasma or serum. provide. See Hassan, M. et. al. Glob Cardiol Sci Pract. 2016 Dec 30; 2016(4): e201634.

In some embodiments, the muscle disease is a muscular dystrophic disease. In some embodiments, the muscular dystrophic disease is Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, or Emery muscular dystrophy. - Dreyfus muscular dystrophy.

In some embodiments, the demyelinating disease is multiple sclerosis, Charcot-Marie-Tooth disease, Perizeus-Merzbacher disease, encephalomyelitis, neuromyelitis optica, adrenoleukodystrophy, or Guillain-Barre syndrome.

In some embodiments, the muscle structural disorder includes Bethlem myopathy, central core disease, congenital muscle fiber asymmetry, distal muscular dystrophy (MD), Duchenne and Becker MD, Emery-Dreifuss MD, facial shoulder Archohumeral type MD, hyaline body myopathy, limb girdle type MD, muscle sodium channel disorder, myotonic chondrodystrophy, myotonic dystrophy, myotubular myopathy, nemaline body disease, eye Pharyngeal MD or stress urinary incontinence.

In some embodiments, the neural activation disorder is amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Guillain-Barre syndrome, Lambert-Eaton syndrome, multiple sclerosis, myasthenia gravis, neurological lesions , peripheral neuropathy, spinal muscular atrophy, delayed ulnar nerve palsy, or toxic muscle neuropathy.

In some embodiments, the muscle wasting disorder is chronic fatigue syndrome, diabetes (type I or type II), glycogen storage disease, fibromyalgia, Friedreich's ataxia, intermittent claudication, lipid storage myopathy, MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) syndrome, mucopolysaccharidosis, Pompe disease or thyrotoxic myopathy.

In some embodiments, the muscle mass disorder is cachexia, cartilage degeneration, cerebral palsy, compartment syndrome, critical disease myopathy, inclusion body myositis, muscular atrophy (disuse), sarcopenia, steroid myopathy, or systemic lupus erythematosus. It is.

In some embodiments, the mitochondrial disease is Alpers disease, chronic progressive external ophthalmoplegia (CPEO), Kearns-Saira syndrome (KSS), Leber hereditary optic neuropathy (LHON), MELAS, myoclonic epilepsy, and ragged red fibers. disease (MERRF), neurogenic muscle weakness (NARP), ataxia, retinitis pigmentosa, Pearson syndrome, mitochondrial dysfunction or loss of mitochondrial function (eg, caused by drugs that affect mitochondrial function).

In some embodiments, the mitochondrial dysfunction is drug-induced mitochondrial dysfunction.

In some embodiments, the beta oxidation disease is a systemic carnitine transporter, carnitine palmitoyltransferase (CPT) II deficiency, very long chain acyl-CoA dehydrogenase (LCHAD or VLCAD) deficiency, trienzyme deficiency, chain acyl-CoA dehydrogenase (MCAD) deficiency, short chain acyl-CoA dehydrogenase (SCAD) deficiency or riboflavin-responsive disorder of β-oxidation (RR-MADD).

In some embodiments, the metabolic disease is hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, HDL hypocholesterolemia, LDL hypercholesterolemia, HLD noncholesterolemia, VLDL Hyperproteinemia, dyslipoproteinemia, apolipoprotein A-I hypoproteinemia, atherosclerosis, arteriosclerosis disease, cardiovascular disease, cerebrovascular disease, peripheral circulatory system disease, metabolic syndrome, Syndrome Liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), blood clots, Alzheimer's disease, neurodegenerative diseases, demyelinating diseases, multiple sclerosis, adrenoleukodystrophy, dermatitis, psoriasis, acne, skin aging, hirsutism disease, inflammation, arthritis, asthma, irritable bowel syndrome, ulcerative colitis, Crohn's disease, or pancreatitis.

In some embodiments, the invention provides a method of treating or preventing sepsis comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. I will provide a. In some embodiments, sepsis is septic shock.

In some embodiments, the invention provides a method of treating or preventing a thrombotic disorder comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, the thrombotic disorder is a high concentration of fibrinogen in the subject's plasma or serum, or enhanced fibrinolytic activity.

In some embodiments, the invention provides a method of treating or preventing obesity comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. I will provide a. In some embodiments, the obesity is abdominal obesity. In some embodiments, the method of treating or preventing obesity further comprises promoting weight loss in the subject.

In some embodiments, the invention provides a method of treating or preventing diabetic nephropathy comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method including. In some embodiments, the method of treating or preventing diabetic nephropathy further comprises treating or preventing kidney disease that develops as a result of diabetes. In some embodiments, the invention provides a method of treating or preventing diabetes comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. I will provide a.

In some embodiments, the invention provides a method of treating or preventing diabetic retinopathy comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method including. In some embodiments, the method of treating or preventing diabetic retinopathy results in the treatment or prevention of complications of diabetes that can result in or are at risk of causing blindness.

In some embodiments, the invention provides a method of treating or preventing cerebrovascular disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the cerebrovascular disease is cerebral ischemia.

In some embodiments, the invention provides a method of treating or preventing a disorder associated with angiogenesis, comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. A method is provided that includes the steps of: In some embodiments, the angiogenesis-related disorder is retinopathy or diabetes.

In some embodiments, the invention provides a method of treating or preventing hypertension comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. I will provide a. In some embodiments, a method of treating or preventing hypertension results in treating or preventing blood flow flowing through a blood vessel in a subject with a force greater than normal.

In some embodiments, the invention provides a method of treating or preventing cancer comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, the cancer is a human sarcoma or human cancer. In some embodiments, the cancer is fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, Synoviomas, mesothelioma, Ewing tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, pancreatic cancer, bone cancer, breast cancer, ovarian cancer, prostate cancer, esophageal cancer, oral cancer, nasal cavity cancer Cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, Cholangiocarcinoma, choriocarcinoma, seminoma, embryonic cancer, Wilms tumor, cervical cancer, uterine cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, epithelial cancer, glioma, astrocytoma , medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic schwannoma, oligodendroglioma, meningioma, skin cancer, melanoma, neuroblastoma, retinoblastoma leukemia, acute B-cell lymphoblastic leukemia, acute T-cell lymphoblastic leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia Cytic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia, acute undifferentiated leukemia, chronic myeloid leukemia, hairy cell leukemia, lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, myeloid leukemia, polycythemia vera, multiple myeloma, lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, Waldenström's macroglobulinemia, or heavy chain disease.

In some embodiments, the leukemia is acute or chronic lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, lymphocytic leukemia, or myeloid leukemia. In some embodiments, the myeloid leukemia is acute and is myeloblastic leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia, or erythroleukemia.

In some embodiments, the lymphoma is Hodgkin's lymphoma or non-Hodgkin's lymphoma.

In some embodiments, the invention provides a method of treating or preventing an inflammatory disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the inflammatory disease is multiple sclerosis, chronic inflammatory disorders of the joints, arthritis, respiratory distress syndrome, inflammatory bowel disease, inflammatory lung disorders, inflammatory disorders, gingival inflammatory disorders, tuberculosis, leprosy, inflammatory diseases of the kidneys, inflammatory disorders of the skin, inflammatory diseases of the central nervous system, systemic lupus erythematosus (SLE) or inflammatory diseases of the heart.

In some embodiments, the arthritis is rheumatoid arthritis or osteoarthritis.

In some embodiments, the inflammatory bowel disease is ileitis, ulcerative colitis or Crohn's disease.

In some embodiments, the inflammatory lung disorder is asthma or chronic obstructive airway disease.

In some embodiments, the ocular inflammatory disorder is corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis, or endophthalmitis.

In some embodiments, the gingival inflammatory disorder is periodontitis or gingivitis.

In some embodiments, the renal inflammatory disease is glomerulonephritis or nephrosis.

In some embodiments, the inflammatory skin disorder is acne, sclerosing dermatitis, psoriasis, eczema, photoaging, or wrinkles.

In some embodiments, the central nervous system inflammatory disease is AIDS-related neurodegeneration, stroke, neurotrauma, Alzheimer's disease, encephalomyelitis, or viral or autoimmune encephalitis.

In some embodiments, the cardiac inflammatory disease is cardiomyopathy.

In some embodiments, the invention provides a method of treating or preventing a neurodegenerative disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the neurodegenerative disease is Alzheimer's disease or Huntington's disease.

In some embodiments, the invention provides a method of treating or preventing an autoimmune disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the autoimmune disease is immune complex vasculitis, systemic lupus or erythematodes.

In some embodiments, the invention provides a method of treating or preventing a neoplastic disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the neoplastic disease is carcinogenesis.

In some embodiments, the invention provides a method of treating or preventing cholestasis comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method.

In some embodiments, the cholestasis is an intrahepatic cholestatic disease or an extrahepatic cholestatic disease. In some embodiments, the intrahepatic cholestatic disease is primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC), or Alagille syndrome (AS). In some embodiments, the method of treating or preventing intrahepatic cholestatic disease provides for a person who may be susceptible to intrahepatic cholestatic disease, but does not experience symptoms of intrahepatic cholestatic disease. , or in a subject that does not exhibit this, prevention of the development of, or reduction in the risk of, intrahepatic cholestatic disease is effected, e.g., clinical symptoms of intrahepatic cholestatic disease are not caused (i.e., prevention). In some embodiments, the method of treating or preventing intrahepatic cholestatic disease comprises inhibiting intrahepatic cholestatic disease, e.g., halting or reducing the development of intrahepatic cholestatic disease. , or reducing the number, frequency, duration or severity of one or more of its clinical symptoms.

In some embodiments, the invention provides a method of treating or preventing an eye disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, the eye disease is dry eye, meibomian gland dysfunction, corneal and conjunctival epithelial disorders, corneal epithelial disorders, or corneal ulcers. In some embodiments, the eye disease is an ocular allergic disease associated with a corneal pathology, such as dry eye syndrome, corneal ulcer, superficial punctate keratitis, corneal epithelial erosion, vernal conjunctivitis, or atopic keratoconjunctivitis. In some embodiments, the eye disease is hyperevaporative dry eye. In some embodiments, the eye disease is damage to corneal epithelial cells. In some embodiments, corneal epithelial cell damage is associated with an endogenous disease, such as Sjögren's syndrome, Stevens-Johnson syndrome, keratoconjunctivitis sicca (dry eye), and the like. In some embodiments, corneal epithelial cell injury is associated with extrinsic diseases such as postoperatively, drug use, trauma, corneal ulcers, meibomianitis, and while wearing conduct lenses. In some embodiments, damage to corneal epithelial cells is associated with ocular allergic diseases associated with corneal lesions, such as vernal conjunctivitis, atopic keratoconjunctivitis, and the like. In some embodiments, the eye disease is superficial punctate keratitis and corneal epithelial erosion.

In some embodiments, the method of treating or preventing an eye disease promotes proliferation of meibomian gland epithelial cells and corneal epithelial cells.

In some embodiments, the invention provides a method of treating or preventing a lysosomal storage disorder comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. Provide a method for including. In some embodiments, the lysosomal storage disorder is neuronal ceroid lipofuscinosis, Alzheimer's disease, Huntington's disease, amyotrophic spinal lateral sclerosis (ALS), Parkinson's disease, multiple system atrophy (MSA), progressive nuclear Superior paralysis (PSP), corticobasal degeneration (CBD), dementia due to Lewy bodies (DLB), autophagy pathway disorder, Tea-Sachs disease, Fabry disease, Niemann-Pick disease, Gaucher disease, Hunter syndrome, Alpha - mannosidosis, aspartylglucosaminuria, cholesterol ester storage disease, chronic hexosaminidase A deficiency, cystinosis, Danon's disease, Faber's disease, fucoidosis, galactosialidosis or Batten's disease.

In some embodiments, the invention provides a method of treating or preventing kidney disease comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, the kidney disease is renal ischemia reperfusion injury. In some embodiments, the kidney disease is acute kidney injury. In some embodiments, the method of treating or preventing kidney disease results in a reduction in a subject's risk for acute kidney injury following coronary artery bypass grafting, transplantation, and/or valve surgery.

In some embodiments, the subject has AKI. In other embodiments, the subject is at risk for AKI.

AKI can be characterized by a rapid decline in renal function, which is caused by several factors such as reduced renal blood flow, glomerulonephritis, use of nephrotoxic antibiotics, use of anticancer drugs, and sepsis. can be caused by.

For example, acute kidney injury can be diagnosed if a subject exhibits changes in one or more of serum creatinine levels, glomerular filtration rate, or urine output. For example, AKI can be characterized by a serum creatinine level that is at least 1.5 times baseline, where baseline refers to the subject's serum creatinine level up to 7 days prior. For example, a patient with AKI can have a serum creatinine level of 1.5-1.9 times baseline, 2.0-2.9 times baseline, or 3.0 times baseline or more. . Alternatively, AKI can be characterized by an increase in serum creatinine of at least 0.3 mg/dL or at least 0.4 mg/dL, such as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours.

Alternatively, AKI can be characterized by a glomerular filtration rate of less than 90 mL/min/1.73 ^m2 . For example, a subject with AKI may have 60-89 mL/min/1.73 m ² , 30-59 mL/min/1.73 m ² , 15-29 mL/min/1.73 m ² , or 15 mL/min/1.73 m 2 . It can have a glomerular filtration rate of less than 73 ^m2 .

Alternatively, AKI has a urine output of less than 0.5 mL/Kg in 6 hours, less than 0.5 mL/Kg in 12 hours, less than 0.3 mL/Kg in 12 hours, or anuria for more than 12 hours. Can be characterized by subject.

AKI can be classified using the KDIGO diagnostic criteria (Kidney Disease Improving Global Outcomes. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements 2012; 2: 1-138), shown in Table 12. .

AKI is associated with specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic kidney disease); non-specific conditions (e.g., ischemia, toxic insults); and extrarenal pathologies (e.g., prerenal may occur with azotemia and acute postrenal obstructive kidney injury). More than one of these conditions can coexist in the same subject, and more importantly, epidemiological evidence shows that even mild reversible AKI has significant clinical consequences, including an increased risk of death. There is support for the view that it has significant consequences. Moreover, the symptoms and clinical consequences of AKI can be completely similar regardless of whether the etiology is primarily intrarenal or due to external stress exerted on the kidneys, so AKI Includes both direct injury to the kidneys and acute impairment of function.

In some embodiments, the subject having AKI or at risk for AKI has diabetes, underlying renal insufficiency, nephritic syndrome, atherosclerotic disease, sepsis, hypotension, hypoxia, myoglobinuria. - Have hematuria or liver disease. In some embodiments, the subject is elderly, pregnant, a surgical patient, or has been exposed to a nephrotoxic agent. In certain embodiments, the subject having or at risk for AKI is a surgical patient. Thus, in certain embodiments, compounds of the present disclosure are administered to surgical patients after surgery, for example, after cardiovascular treatment, such as coronary artery bypass graft (CABG) surgery and/or heart valve surgery.

In some embodiments, the subject has sepsis (eg, associated with a Gram-negative infection). Sepsis, in some embodiments, can be caused by an intraperitoneal infection or can be urinary sepsis. Sepsis is a risk factor for AKI. Thus, in some embodiments, the subject may be at risk for AKI due to sepsis, for example.

In some embodiments, the subject has a Shortened Sequential Organ Failure Assessment Score (SOFA) of 1 to 4, such as a score of 1, 2, 3 or 4 (Vincent et al. al. 1996, Intensive Care Med, 22:707-710).

In some embodiments, the subject has or is at risk for AKI secondary to an infection, eg, due to a viral infection, eg, COVID-19.

In some embodiments, the subject having AKI or at risk for AKI has been exposed to a nephrotoxic agent. Nephrotoxic agents are drugs or chemicals that can cause AKI. Drugs or chemicals that can cause AKI include, but are not limited to, cisplatin; gentamicin; cephaloridine; cyclosporin; amphotericin; carbon tetrachloride; trichlorethylene; and dichloroacetylene.

In some embodiments, the invention provides a method of treating or preventing erectile dysfunction comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. provide a method. In some embodiments, erectile dysfunction is caused by damage to nerves, arteries, smooth muscle or fibrous tissue; diabetes; kidney disease; alcoholism; multiple sclerosis; atherosclerosis; vascular disease; or neurological Due to disease. In some embodiments, methods of treating or preventing erectile dysfunction result in the treatment or prevention of erectile dysfunction.

The present invention provides a method for treating or preventing dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, or dyslipidemia, and provides a method for treating or preventing dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, or abnormal lipid metabolism, and for a subject in need thereof. A method is provided comprising administering an effective amount of a compound of the invention or a composition of the invention. In some embodiments, the hypercholesterolemia is homozygous familial hypercholesterolemia.

The present invention detects abnormally high concentrations of high-low-density lipoprotein (LDL), apolipoprotein B (apoB), lipoprotein (a) (Lp(a)), and apolipoprotein (a) in the plasma or serum of a subject. or very low density lipoprotein (VLDL), or a method of preventing a subject from having abnormally high levels of the same, comprising administering to a subject in need thereof an effective amount of the present invention. or a composition of the invention.

An "abnormally high concentration" of lipoprotein-cholesterol may depend on the number of risk factors and whether the treatment is for primary or secondary prevention. As used herein, "primary prevention" refers to treatment aimed at preventing a subject from developing or acquiring a disease or condition. As used herein, "secondary prevention" refers to treatment aimed at early detection of a disease or condition and preventing the disease or condition from worsening or progressing. Recommended lipoprotein-cholesterol concentrations are recommended by the National Lipid Association, such as the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report), 2002, or by the National Institute of Health. Guidelines published by the National Heart, Lung, and Blood Institute can be found in the guidelines published by the National Heart, Lung, and Blood Institute. The ATP III Final Report is incorporated herein by reference in its entirety for all purposes.

In some embodiments, the invention provides a method of reducing abnormally high concentrations of apoB in the plasma or serum of a subject, comprising: administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising administering a composition of the invention. In some embodiments, an "abnormally high concentration" of apoB in a subject's plasma or serum is greater than 130 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of apoB in the subject's plasma or serum is less than 130 mg/dL. In some embodiments, the subject is a male subject. In some embodiments, the subject is a female subject. In some embodiments, the invention provides methods of treating a subject with a plasma or serum concentration of apoB greater than 130 mg/dL. In some embodiments, the invention provides a method for controlling plasma apoB of greater than 130 mg/dL when the subject is at low risk for coronary heart disease (CHD) and has CHD risk factors of 0-1. A method of treating a subject having a concentration or serum concentration is provided.

In some embodiments, the invention provides plasma or serum concentrations of apoB greater than 110 mg/dL when the subject is at moderate risk for CHD and has two or more CHD risk factors. Provided are methods for treating subjects with. In some embodiments, an "abnormally high concentration" of apoB in a subject's plasma or serum is greater than 110 mg/dL. In some embodiments, the subject has two or more CHD risk factors. In some embodiments, the subject has CHD or is at risk for CHD. In some embodiments, the invention provides methods of treating a subject who has a plasma or serum concentration of apoB greater than 90 mg/dL if the subject has CHD, or is at risk for CHD. .

In some embodiments, the invention provides a method of reducing abnormally high concentrations of Lp(a) in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the invention. Alternatively, a method is provided comprising the step of administering a composition of the invention. An "abnormally high concentration" of Lp(a) in a subject's plasma or serum is greater than 10 mg/dL. In some embodiments, abnormally high concentrations of Lp(a) are associated with increased cardiovascular risk. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of Lp(a) in the subject's plasma or serum is less than 10 mg/dL. In some embodiments, the normal concentration of Lp(a) in the subject's plasma or serum is less than 50 mg/dL (see Banach, M. J Am Heart Assoc. 2016 Apr; 5(4): e003597). sea bream). In some embodiments, the invention provides a method of treating a subject with a plasma concentration of Lp(a) greater than 50 mg/dL, comprising administering to the subject in need thereof an effective amount of a compound of the invention. Alternatively, a method is provided comprising the step of administering a composition of the invention.

The present invention is a method of treating a subject having an abnormally high apoB/apoA-I ratio in the subject's plasma or serum, or preventing a subject from having an abnormally high apoB/apoA-I ratio, in need thereof. A method is provided comprising administering to a subject an effective amount of a compound of the invention or a composition of the invention. In some embodiments, the present invention provides a method for reducing an abnormally high apoB/apoA-I ratio in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of the present invention. or a composition of the invention. An "abnormally high" apoB/apoA-I ratio in a subject's plasma or serum is greater than 0.9. In some embodiments, the reduction is to normal levels. In some embodiments, the normal apoB/apoA-I ratio in the subject's plasma or serum is less than 0.9. In some embodiments, a normal apoB/apoA-I ratio in the subject's plasma or serum is less than 0.7. In some embodiments, the subject has an apoB/apoAI ratio greater than 0.9 in the subject's plasma or serum. In some embodiments, the subject has an apoB/apoAI ratio greater than 0.7 in the subject's plasma or serum. See Walldius, G. et al. J Intern Med. 2006 May;259(5):493-519.

In some embodiments, a male subject who has an apoB/apoA-I ratio greater than 0.9 in the male subject's plasma or serum is considered for primary prevention treatment. In some embodiments, a female subject who has an apoB/apoA-I ratio greater than 0.8 in the female subject's plasma or serum is considered for primary prevention treatment. In some embodiments, the subject is a male subject and has an apoB/apoAI ratio greater than 0.9 in the subject's plasma or serum. In some embodiments, the subject is a female subject and has an apoB/apoAI ratio greater than 0.8 in the subject's plasma or serum. See Walldius, 2006.

In some embodiments, a male subject who has an apoB/apoA-I ratio greater than 0.7 in the male subject's plasma or serum is considered for secondary prevention treatment. In some embodiments, a female subject who has an apoB/apoA-I ratio greater than 0.6 in the female subject's plasma or serum is considered for secondary prevention treatment. In some embodiments, the subject is a male subject and has an apoB/apoAI ratio greater than 0.7 in the subject's plasma or serum. In some embodiments, the subject is a female subject and has an apoB/apoAI ratio greater than 0.6 in the subject's plasma or serum. See Walldius, 2006.

The present invention is a method of treating a subject with, or preventing a subject from having, an abnormally low concentration of high-density lipoprotein (HDL) in the subject's plasma or serum, comprising: A method is provided comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention provides a method for treating a subject having, or preventing a subject from having, an abnormally reduced or deficient lipoprotein lipase concentration or activity in the subject's plasma or serum, the subject in need thereof The method comprises administering an effective amount of a compound of the invention or a composition of the invention. In some embodiments, a reduction or deficiency in lipoprotein lipase levels or activity is the result of a lipoprotein lipase mutation. In some embodiments, a reduction or deficiency in lipoprotein lipase levels or activity is the result of a mutation in the gene encoding lipoprotein lipase.

In some embodiments, the invention provides a method for improving abnormally low concentrations of lipoprotein lipase in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the invention or A method is provided comprising administering a composition of the invention. An "abnormally reduced" concentration of lipoprotein lipase in a subject's serum is less than 46 ng/mL. In some embodiments, the subject has an increased risk of future coronary artery disease. In some embodiments, the increase is to normal concentrations. In some embodiments, a normal concentration of lipoprotein lipase in a subject's serum is greater than 46 ng/mL. In some embodiments, the invention provides a method of treating a subject with a plasma or serum concentration of lipoprotein lipase of less than 46 ng/mL, comprising: administering an effective amount of the present invention to a subject in need thereof; A method is provided comprising administering a compound of the invention or a composition of the invention. See Rip, J. et al. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):637-42. Epub 2005 Dec 22.

The present invention provides a method of treating a subject with an abnormally high concentration of lipoprotein-associated phospholipase A ₂ (Lp-PLA ₂ ) in the subject's plasma or serum, or preventing a subject from having an abnormally high concentration of A method of administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention is provided. An "abnormally high concentration" of Lp-PLA ₂ in a subject's plasma or serum is greater than 200 ng/mL. In some embodiments, the subject is at risk of developing cardiovascular disease. In some embodiments, the risk is high.

In some embodiments, the invention provides a method of reducing abnormally high concentrations of Lp-PLA ₂ in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the invention. Alternatively, a method is provided comprising the step of administering a composition of the invention. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of Lp-PLA ₂ in the subject's plasma or serum concentration is less than 200 ng/mL. In some embodiments, the invention provides methods of treating a subject with an Lp-PLA ₂ plasma or serum concentration greater than 200 ng/mL. See Davidson, MH et al, The American Journal of Cardiology, 2008, 101, S51.

The present invention provides a method for treating or preventing hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial combined hyperlipidemia. and administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

The present invention detects abnormally high concentrations of triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and non-high-density lipoprotein cholesterol (non-high-density lipoprotein cholesterol) in the plasma or serum of a subject. HDL-C), lipoprotein (a) (Lp(a)), apolipoprotein B, HDL/(VLDL+LDL) ratio, apolipoprotein C-II (apoC-II) or apolipoprotein C-III (apoC-III ) is provided, the method comprising the step of administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention.

An "abnormally high concentration" of triglycerides in a subject's serum is greater than 150 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of triglycerides in the subject's serum is less than 150 mg/dL. In some embodiments, the invention provides a method of reducing serum triglyceride concentration in a subject, wherein the subject has a serum triglyceride concentration of 200 mg/dL or greater. In some embodiments, the invention provides a method of reducing serum triglyceride concentration in a subject, wherein the subject has a serum triglyceride concentration of 500 mg/dL or greater.

For primary prevention, an "abnormally high concentration" of LDL-C in a subject's plasma or serum is greater than 100 mg/dL. For secondary prevention, an "abnormally high concentration" of LDL-C in a subject's plasma or serum is greater than 70 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the subject's normal concentration of LDL-C in plasma or serum is less than 100 mg/dL and the subject is considered for primary prophylaxis. In some embodiments, the normal concentration of LDL-C in the subject's plasma or serum is less than 70 mg/dL. In some embodiments, the subject has a risk factor and secondary prevention is considered. See Walldius, 2006.

In some embodiments, an "abnormally high concentration" of LDL-C in a subject's plasma or serum is greater than 160 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of LDL-C in the subject's plasma or serum is less than 160 mg/dL. In some embodiments, the subject has a CHD risk factor of 0-1. In some embodiments, the invention provides methods of treating a subject with a plasma or serum LDL-C concentration greater than 160 mg/dL. In some embodiments, the invention provides methods of treating a subject with a plasma or serum LDL-C concentration greater than 160 mg/dL. In some embodiments, the subject has a CHD risk factor of 0-1. See Walldius, 2006.

In some embodiments, an "abnormally high concentration" of LDL-C in a subject's plasma or serum is greater than 130 mg/dL. In some embodiments, the subject has two or more CHD risk factors. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of LDL-C in the subject's plasma or serum is less than 130 mg/dL. In some embodiments, the subject has two or more CHD risk factors. In some embodiments, the invention provides methods of treating a subject with a plasma or serum LDL-C concentration greater than 130 mg/dL. In some embodiments, the subject has two or more CHD risk factors. See Walldius, 2006.

In some embodiments, an "abnormally high concentration" of LDL-C in a subject's plasma or serum is greater than 100 mg/dL. In some embodiments, the subject has CHD or is at risk for CHD. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of LDL-C in the subject's plasma or serum is less than 100 mg/dL. In some embodiments, the subject has CHD or is at risk for CHD. In some embodiments, the invention provides methods of treating a subject with a plasma or serum LDL-C concentration greater than 100 mg/dL. In some embodiments, the subject has CHD or is at risk for CHD. See Walldius, 2006.

An "abnormally high concentration" of apoC-III in a subject's plasma or serum is greater than 7.87 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of apoC-III in the subject's plasma or serum is less than 7.87 mg/dL. In some embodiments, the invention provides a method of treating a subject, wherein the subject has a plasma or serum apoC-III concentration greater than 8 mg/dL. In some embodiments, the invention provides a method of treating a subject, wherein the subject has a plasma or serum apoC-III concentration greater than 7.9 mg/dL. In some embodiments, the invention provides a method of treating a subject, wherein the subject has a plasma or serum apoC-III concentration greater than 7.87 mg/dL. In some embodiments, abnormally high concentrations of apoC-III are associated with increased risk of coronary artery disease. See Capelleveen et al. Arterioscler Thromb Vasc Biol. 2017 Jun; 37(6): 1206-1212.

The present invention provides a method for lowering an abnormally high LDL-C/HDL-C ratio in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the present invention or a composition of the present invention. A method is provided comprising the step of administering an agent.

In some embodiments, for primary prevention, an "abnormally high ratio" of LDL-C/HDL-C in the plasma or serum of a male subject is greater than 3.0. In some embodiments, the reduction is to normal. In some embodiments, the male subject's normal ratio of LDL-C/HDL-C in plasma or serum is less than 3.0 and the subject is considered for primary prevention. In some embodiments, the invention provides methods of treating a male subject having an LDL-C/HDL-C ratio greater than 3.0 in his plasma or serum. In some embodiments, the method is for primary prevention.

In some embodiments, an "abnormally high ratio" of LDL-C/HDL-C in the plasma or serum of a female subject for primary prevention is greater than 2.5. In some embodiments, the reduction is to normal. In some embodiments, the female subject's normal ratio of LDL-C/HDL-C in plasma or serum is less than 2.5 and the subject is considered for primary prevention. In some embodiments, the invention provides methods of treating a female subject having an LDL-C/HDL-C ratio greater than 2.5 in their plasma or serum. In some embodiments, the method is for primary prevention. See Walldius, 2006.

In some embodiments, for secondary prevention, an "abnormally high ratio" of LDL-C/HDL-C in the plasma or serum of a male subject is greater than 2.5. In some embodiments, the reduction is to normal. In some embodiments, the male subject's normal ratio of LDL-C/HDL-C in plasma or serum is less than 2.5 and the subject is considered for secondary prevention. In some embodiments, the invention provides a method of treating a male subject having an LDL-C/HDL-C ratio greater than 2.5 in his plasma or serum. In some embodiments, the method is for secondary prevention. See Walldius, 2006.

In some embodiments, for secondary prevention, an "abnormally high ratio" of LDL-C/HDL-C in the plasma or serum of a female subject is greater than 2.0. In some embodiments, the reduction is to normal. In some embodiments, the female subject's normal ratio of LDL-C/HDL-C in plasma or serum is less than 2.0 and the subject is considered for secondary prevention. In some embodiments, the invention provides methods of treating a female subject having an LDL-C/HDL-C ratio greater than 2.0 in their plasma or serum. In some embodiments, the method is for secondary prevention. See Walldius, 2006.

The present invention provides a method for reducing abnormally high concentrations of non-HDL-C in the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of the present invention or a composition of the present invention. A method is provided comprising the step of administering.

In some embodiments, an "abnormally high concentration" of non-HDL-C in a subject's plasma or serum is greater than 190 mg/dL. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of non-HDL-C in the subject's plasma or serum is less than 190 mg/dL. In some embodiments, the subject has a CHD risk factor of 0-1. In some embodiments, the invention provides a method of reducing a subject's non-HDL-C concentration in the subject's plasma or serum, wherein the non-HDL-C concentration is greater than 190 mg/dL. In some embodiments, the subject has a CHD risk factor of 0-1. See Walldius, 2006.

In some embodiments, an "abnormally high concentration" of non-HDL-C in a subject's plasma or serum is greater than 160 mg/dL. In some embodiments, the subject has two or more CHD risk factors. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of non-HDL-C in the subject's plasma or serum is less than 160 mg/dL. In some embodiments, the subject has two or more CHD risk factors. In some embodiments, the invention provides a method of reducing a subject's non-HDL-C concentration in the subject's plasma or serum, wherein the subject's non-HDL-C concentration is greater than 160 mg/dL. do. In some embodiments, the subject has two or more CHD risk factors. See Walldius, 2006.

In some embodiments, an "abnormally high concentration" of non-HDL-C in a subject's plasma or serum is greater than 130 mg/dL. In some embodiments, the subject has CHD or is at risk for CHD. In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of non-HDL-C in the subject's plasma or serum is less than 130 mg/dL. In some embodiments, the subject has CHD or is at risk for CHD. In some embodiments, the invention provides a method of reducing a subject's non-HDL-C concentration in the subject's plasma or serum, wherein the subject's non-HDL-C concentration is greater than 130 mg/dL. do. In some embodiments, the subject has CHD or is at risk for CHD. See Walldius, 2006.

The present invention provides a method for improving abnormally low levels of high-density lipoprotein (HDL)-related protein, HDL-cholesterol (HDL-C), apolipoprotein AI, or apolipoprotein E in the plasma or serum of a subject. and administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. In some embodiments, the HDL-associated protein is apolipoprotein AI (apoA-I), apolipoprotein A-II (apoA-II), apolipoprotein A-IV (apoA-IV), or apolipoprotein E (ApoE).

In some embodiments, an "abnormally low concentration" of HDL-C in a subject's plasma or serum is less than 40 mg/dL. In some embodiments, the increase is to normal concentrations. In some embodiments, the normal concentration of HDL-C in the subject's plasma or serum is greater than 40 mg/dL. In some embodiments, the invention provides a method of increasing HDL-C concentration in plasma or serum of a subject, wherein the subject's HDL-C concentration is less than 40 mg/dL. In some embodiments, the subject is a male subject. In some embodiments, the subject is a female subject.

In some embodiments, an "abnormally low concentration" of HDL-C in the plasma or serum of a male subject is less than 45 mg/dL. In some embodiments, the normal concentration of HDL-C in plasma or serum of a male subject is greater than 45 mg/dL. In some embodiments, the invention provides a method of increasing HDL-C concentration in plasma or serum of a male subject, wherein the subject's HDL-C concentration is less than 45 mg/dL.

In some embodiments, an "abnormally low concentration" of HDL-C in the plasma or serum of a female subject is less than 50 mg/dL. In some embodiments, the normal concentration of HDL-C in plasma or serum of a female subject is greater than 50 mg/dL. In some embodiments, the normal concentration of HDL-C in plasma or serum of a female subject is greater than 55 mg/dL. In some embodiments, the invention provides a method of increasing HDL-C concentration in plasma or serum of a female subject, wherein the subject's HDL-C concentration is less than 50 mg/dL. In some embodiments, the invention provides a method of increasing HDL-C concentration in plasma or serum of a female subject, wherein the subject's HDL-C concentration is less than 55 mg/dL.

In some embodiments, the invention provides a method for increasing the concentration of HDL-C in the plasma or serum of a subject to 45 mg/dL or higher, wherein the concentration of HDL-C in the plasma or serum of the subject is 40 mg/dL or more. /dL. In some embodiments, the invention provides a method for increasing the concentration of HDL-C in the plasma or serum of a subject to 50 mg/dL or more, wherein the concentration of HDL-C in the plasma or serum of the subject is 40 mg/dL or more. /dL. In some embodiments, the invention provides a method for increasing the concentration of HDL-C in the plasma or serum of a subject to 55 mg/dL or higher, wherein the concentration of HDL-C in the plasma or serum of the subject is 40 mg/dL or more. /dL.

In some embodiments, the invention provides a method for increasing the HDL-C concentration in the plasma or serum of a male subject to 50 mg/dL or more, wherein the HDL-C concentration in the subject's plasma or serum is 45 mg/dL. In some embodiments, the invention provides a method of increasing HDL-C concentration in the plasma or serum of a female subject to 50 mg/dL or more, wherein the HDL-C concentration of the subject in the plasma or serum of the subject is 50 mg/dL. In some embodiments, the invention provides a method for increasing the HDL-C concentration in the plasma or serum of a female subject to 55 mg/dL or more, wherein the HDL-C concentration in the subject's plasma or serum increases to 55 mg/dL or more. 50 mg/dL.

The present invention is a method of promoting the clearance of triglycerides from the plasma or serum of a subject, the method comprising the step of administering to a subject in need thereof an effective amount of a compound of the present invention or a composition of the present invention. provide a method.

The present invention provides a method for improving abnormally low glucose metabolism or abnormally low lipid metabolism in a subject, the method comprising administering an effective amount of a compound of the present invention or a composition of the present invention to a subject in need thereof. A method is provided that includes the step of administering an agent. In some embodiments, the method of improving abnormally low glucose metabolism increases insulin sensitivity or oxygen consumption in the subject. In some embodiments, the method of improving abnormally low glucose metabolism reduces blood insulin, blood sugar, or glycated hemoglobin in the subject's plasma or serum. In some embodiments, the method of improving abnormally low lipid metabolism reduces the concentration of LDL or free triglycerides or inhibits saponified or unsaponified fatty acid synthesis in the subject's plasma or serum. Ru.

In some embodiments, a subject with abnormally low glucose metabolism has abnormally high concentrations of glucose or hemoglobin (Hb) in the subject's plasma or serum. In some embodiments, the invention provides methods of lowering abnormally high concentrations of glucose or hemoglobin in the plasma or serum of a subject. In some embodiments, the method improves abnormally low glucose metabolism. An "abnormally high concentration" of glucose in a subject's plasma or serum at 2 hours GTT is greater than 7.8 mmol/L (140 mg/dL). In some embodiments, the reduction is to normal concentrations. In some embodiments, the normal concentration of glucose in the subject's plasma or serum at 2 hours GTT is less than 7.8 mmol/L (140 mg/dL). In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in the plasma or serum of a subject, wherein the concentration of glucose in the subject's plasma or serum at 2 hours GTT is 7. 8 mmol/L (140 mg/dL). In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the concentration of glucose in the subject's plasma or serum at 2 hours GTT is 7.8 mmol/L. (140 mg/dL) to 11.1 mmol/L (200 mg/dL). In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the concentration of glucose in the subject's plasma or serum at 2 hours GTT is 11.1 mmol/L ( 200 mg/dL).

In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the subject has impaired glucose tolerance. In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the subject has diabetes. In some embodiments, the invention provides a method of improving abnormally low glucose metabolism in a subject, wherein the subject has gestational diabetes.

Low lipid metabolism can be characterized by dyslipidemia (using values of LDL-C, TG, non-HDL-cholesterol, apoB, apoC-III or apoC-II), while increased concentrations of transaminases It also accompanies. In some embodiments, subjects with low lipid metabolism also have dyslipidemia.

The present invention provides a method for treating or preventing symptoms of a disease selected from inflammation, systemic lupus erythematosus, lupus nephritis, or arthritis, comprising administering to a subject in need thereof an effective amount of a compound of the present invention or a compound of the present invention. A method is provided comprising administering a composition. In some embodiments, the arthritis is adjuvant arthritis or type II collagen-induced arthritis. In some embodiments, the condition is nephritis, renal failure or decreased renal function. In some embodiments, decreased renal function requires renal dialysis.

The invention provides a method for reducing the fat content of meat in livestock, the method comprising administering to the livestock an effective amount of a compound of the invention or a composition of the invention.

The invention provides a method for reducing the cholesterol content of poultry eggs, which method comprises administering to a species of poultry an effective amount of a compound of the invention or a composition of the invention.

In some embodiments, the methods of the invention provide for administering a dosage form of a compound of the invention or a composition of the invention hourly, daily, weekly, or monthly. Dosage forms and formulations of the invention may be administered three times a day, twice a day or once a day. The dosage forms of the invention may be administered with or without food. The appropriate length of treatment, dosage and route of administration may be determined and/or adjusted by the physician.

In some embodiments of the methods of the invention, the subject is a human subject.

5.5. Synthesis of Compounds of the Invention Compounds of the invention can be synthesized by conventional means. Exemplary processes for synthesizing exemplary compounds of Formula (A) and Formula (B) are described in Examples 1-3 below. WO 2011/020001, the entire contents of which are incorporated herein by reference, describes PPAR modulator compounds (described therein as compounds of formulas (I) to (XX)). , and its synthesis process. Compounds of formulas (I) to (XX) described in International Publication No. 2011/020001 pamphlet are obtained by synthesizing compounds of formulas (C) to (H) and (J) to (W) of the present invention, respectively. It can be used as a starting material for For example, the compound of WO 2011/020001 having a ketone can optionally be reduced with a reducing agent such as NaBH ₄ in the presence of a Lewis acid such as CeCl ₃ or in an alcoholic solvent such as methanol to produce a ketone. can result in the conversion of groups to hydroxyl groups. Similarly, the carboxylic acid group of the compound of WO 2011/020001 is reduced to a hydroxymethyl group using a reducing reagent such as _LiAlH4 , and then by post-treatment with acidic water, the compound of the invention is Obtainable.

WO 2017/062468, the entire content of which is incorporated herein by reference, describes PPAR modulator compounds (described therein as compounds of formulas (I) to (III)), and The synthesis process is described. The compounds of formulas (I) to (III) described in International Publication No. 2017/06246 pamphlet are used as starting materials for synthesizing the compounds of formulas (X) to (Z) of the present invention, respectively. be able to. The carboxylic acid group of the compound of WO 2017/06246 pamphlet can be reduced to a hydroxymethyl group using a reducing reagent such as LiAlH ₄ and then post-treatment with acidic water to obtain the compound of the present invention. can.

WO 2017/180818, the entire content of which is incorporated herein by reference, describes PPAR modulator compounds (described herein as compounds of formula (I)) and processes for their synthesis. It is listed. The compound of formula (I) described in WO 2017/180818 pamphlet can be used as a starting material for synthesizing the compound of formula (AA) of the present invention. The carboxylic acid group of the compound of WO 2017/180818 pamphlet can be reduced to a hydroxymethyl group using a reducing reagent such as _LiAlH4 , followed by post-treatment with acidic water to obtain the compound of the present invention. can.

WO 2018/067857, the entire contents of which are incorporated herein by reference, describes PPAR modulator compounds (described herein as compounds A, B and C) and their synthetic processes. It is listed. Compounds B and C described in International Publication No. 2018/067857 pamphlet can be used as starting materials for synthesizing compounds VII and VIII. The carboxylic acid group of the compound of WO 2017/180818 pamphlet can be reduced to a hydroxymethyl group using a reducing reagent such as _LiAlH4 , followed by post-treatment with acidic water to obtain the compound of the present invention. can.

In the case of selective reduction of carboxylic acids in compounds having both ketone and carboxylic acid groups, for example some of the compounds described in WO 2011/020001, the ketone can be reduced in a manner such as 0.1M HCl etc. Protection can be achieved by reacting the compound with ethylene glycol in the presence of an acid catalyst to form an acetal compound. This acetal can be removed after reduction of the carboxylic acid groups, for example by after-treatment with acidic water. In the case of selective reduction of ketones in compounds having both ketone and carboxylic acid groups, for example some of the compounds described in WO 2011/020001, the ketones are less reactive, such as _NaBH4 . Selective reduction can be achieved by using less expensive reducing agents.

6. Example 6.1.
[Example 1]
Synthesis of compound I

（Ｚ）－２－（２，６－ジメチル－４－（３－（４－（メチルチオ）フェニル）－３－オキソプロパ－１－エン－１－イル）フェノキシ）－２－メチルプロパン酸（「化合物Ａ」）は、米国特許出願公開第２００６／０１４２６１１号明細書に準拠して合成する。次に、化合物Ａを、場合により、ＣｅＣｌ_３などのルイス酸の存在下、またはメタノールなどのアルコール溶媒中、ＮａＢＨ_４などの還元剤を使用して還元し、化合物Ｉのラセミ体を得る。次に、キラル高速液体クロマトグラフィーを使用して、化合物Ｉのラセミ体を分割して、その（Ｓ）－および（Ｒ）－鏡像異性体を得て、各々は、その対応する反対の鏡像異性体を実質的に含まない。

(Z)-2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxoprop-1-en-1-yl)phenoxy)-2-methylpropanoic acid (“Compound A'') is synthesized according to US Patent Application Publication No. 2006/0142611. Compound A is then reduced using a reducing agent such as _NaBH4 , optionally in the presence of a Lewis acid such as _CeCl3 , or in an alcoholic solvent such as methanol, to obtain the racemic form of Compound I. The racemic form of Compound I is then resolved using chiral high performance liquid chromatography to obtain its (S)- and (R)-enantiomers, each of which has its corresponding opposite enantiomer. Contains virtually no body.

6.2.
[Example 2]
Synthesis of compound II

アセタール化合物Ｂは、０．１Ｍ ＨＣｌなどの酸触媒の存在下、化合物Ａおよびエチレングリコールから合成する。アセタール形成、特にα，β－不飽和ケトンに関しては、例えば、Dong, J-L., et al. ACS Omega, 2018, 3, 4974を参照されたい。化合物Ｂのカルボキシル基は、続いて、ＬｉＡｌＨ_４などの還元試薬を使用してヒドロキシメチル基に還元し、次いで、酸性水によって後処理し、これによってアセタールを除去して、化合物ＩＩを得る。

Acetal Compound B is synthesized from Compound A and ethylene glycol in the presence of an acid catalyst such as 0.1M HCl. Regarding acetal formation, especially α,β-unsaturated ketones, see, for example, Dong, JL., et al. ACS Omega, 2018, 3, 4974. The carboxyl group of compound B is subsequently reduced to a hydroxymethyl group using a reducing reagent such as LiAlH ₄ and then worked up with acidic water, thereby removing the acetal to yield compound II.

6.3.
[Example 3]
Synthesis of compound III

化合物ＩＩを、場合により、ＣｅＣｌ_３などのルイス酸の存在下、またはメタノールなどのアルコール溶媒中、ＮａＢＨ_４などの還元剤により還元して、化合物ＩＩＩのラセミ体を得る。次に、キラル高速液体クロマトグラフィーを使用して、化合物ＩＩＩのラセミ体を分割して、その（Ｓ）－および（Ｒ）－鏡像異性体を得、各々は、その対応する反対の鏡像異性体を実質的に含まない。

Compound II is optionally reduced with a reducing agent such as NaBH ₄ in the presence of a Lewis acid such as CeCl ₃ or in an alcoholic solvent such as methanol to give the racemate of compound III. The racemate of compound III is then resolved using chiral high performance liquid chromatography to obtain its (S)- and (R)-enantiomers, each of which is separated from its corresponding opposite enantiomer. Contains virtually no.

6.4.
[Example 4]
Hepatic and peripheral insulin sensitivity effects in rats fed a high fat/moderate fructose diet (Western style diet) After 8 weeks of high fat diet, rats were treated with pioglitazone (10 mg/kg) alone, metformin (50 mg/kg) ), by the exemplary compounds of the present invention (3 and 10 mg/kg), or by metformin (50 mg/kg) and GW501516 (2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl ) phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid) (10 mg/kg; ligand/GSK) for 5 weeks. Body weight can be lowered by metformin, and this effect can be accentuated when combined with a dose of 10 mg/kg of an exemplary compound of the invention. After 17 days of treatment, rats are fasted for 4 hours and blood is sampled.

Glucose tolerance is assessed 21 days after treatment by oral glucose load after a 6 hour fast.

After 5 weeks of treatment, conscious rats undergo a hyperinsulinemic euglycemic clamp procedure. Two doses of insulin are infused with H-glucose: 0.2 U/kg/hr to assess the effect on hepatic glucose production (HGP) and 0.8 U/kg/hr to inhibit HGP. , and then to evaluate the effect on whole-body glucose utilization.

6.4.1. Animal Model To induce insulin resistance, male Sprague Dawley (SD) rats (250-275 g) are initially fed a Western-style diet for 8 weeks. The first set of rats underwent an oral glucose tolerance test (OGTT) (half rats/clamp treatment group) three weeks after treatment, and the second set also underwent an OGTT (half rats/clamp treatment group) three weeks after treatment. /clamp arm treatment group) and undergo histological examination (3 rats/group).

Each set of rats was screened and divided into several groups based on their fasting (4 hour) plasma glucose, insulin levels (for homeostasis model assessment of insulin resistance (HOMA-IR) calculations), and body weight. Be intentional. Rats that do not respond to Western-style diet will be excluded from this study.

Homogeneous mildly obese and insulin resistant rats are assigned to different groups and maintained on a Western-style diet until the end of the experiment. Assume starting with two strains, one week apart.

6.4.2. Treatment Dosage regimen: Rats are treated once daily by oral route in the morning. The duration of this treatment is between 5 and 5.5 weeks.

6.4.3. Test Group Group 1: Vehicle (n=12)
Group 2: pioglitazone, 10 mg/kg (n=12)
Group 3: Metformin, 50mg/Kg (n=12)
Group 4: Exemplary compound of the present invention 3 mg/Kg (n=12)
Group 5: Exemplary compound of the present invention 10 mg/Kg (n=12)
Group 6: Exemplary compound of the present invention 3 mg/Kg + metformin 50 mg/kg (n=12)
Group 7: Exemplary compound of the present invention 10 mg/Kg + metformin 50 mg/kg (n=12)
Group 8: GW501216, 10mg/Kg (n=12)

6.4.4. Fasting conditions Fasting conditions and clamp procedures for OGTT: Change the litter (between 7:30 am and 8:00 am) just before removing food from the cage and turning off lights. Each experiment is then started after approximately 6 hours of fasting (between 1:30 and 2:00 pm).

Fasting conditions for plasma parameters: food is removed from the cage, lights are turned off and litter is changed after 4 hours (between 11:30 am and noon). Next, blood collection is started after 4 hours of fasting (4:00 pm).

6.4.5. Oral Glucose Tolerance Test After 3 weeks of treatment, rats are fasted for 6 hours and subjected to oral glucose tolerance (2.5 g/kg body weight). Blood glucose is measured 30 minutes before the glucose load and at 0, 15, 30, 60, 90 and 120 minutes.

6.4.6. Hyperinsulinemic euglycemic two-step clamp with 3H-glucose Four weeks after the procedure, a catheter is implanted in the femoral vein under isoflurane anesthesia and a 5-6 day period is allowed for recovery. Rats that do not regain weight will be excluded from this study. Estimated weight loss tolerance on the day of perfusion was observed in groups in which treatment should not affect body weight (observed during body weight follow-up) (vehicle, pioglitazone and exemplified compounds of the invention, mg/kg groups) and fixed at 10% for groups that lose weight due to treatment (the other 5 groups). On the morning of the clamp procedure, rats are treated and fasted for 6 hours before infusion of tracer, glucose and insulin. The start of the clamp procedure is at the midpoint of the dark cycle.

A hyperinsulinemic euglycemic two-step insulin clamp is performed using 0.2 U/kg/hr and 0.8 U/kg/hr insulin infusions together with 3H-glucose infusion. From now on, evaluate the following parameters:
Whole body glucose utilization Hepatic glucose production Glucose infusion Whole body glycogen and glycolytic rate

6.4.7. In Vivo Glucose Rate During the clamp procedure, a bolus of D-[3-3H]glucose (30 μCi) was first injected, then 4 μCi/min/kg during all experiments, with no detectable plasma Ensure medium D[3-3H]glucose enrichment. Inject a bolus of insulin (100 mU) first, then inject insulin at a rate of 0.2 U/kg/hour for the first 2 hours, and 0.8 U/kg/hour from 120 minutes to 210 minutes. .

During the infusion period, if necessary, assess glycemia using a blood glucose meter from the tip of the tail vein. Euglycemic levels are maintained by periodically (every 10 minutes) adjusting various infusion volumes of 30% glucose. During the plateau period, plasma Determine intermediate glucose concentration and D-[3-3H]glucose specific activity.

Regarding the measurement of glucose turnover, D-[3-3H]glucose enrichment is determined from whole blood after deproteinization by Zn(OH) ₂ precipitation. Briefly, an aliquot of the supernatant is evaporated to dryness and the radioactivity corresponding to D-3-3H determined. In a second aliquot of the same supernatant, the glucose concentration is assessed by the glucose oxidase method (Biomerieux, France).

6.4.8. Calculations Calculations of glucose turnover measurements are performed from the parameters obtained during the infusion at steady state conditions (60-120 and 160-210 minutes). Briefly, D-[3-3H]glucose specific activity is calculated by dividing the D-[3-3H]glucose enrichment by the plasma glucose concentration. Whole body glucose turnover rate is calculated by dividing the amount of D[3-3H]glucose by the plasma specific activity of D-[3-3H]glucose. For each rat, calculate the mean value and average the values from the same group of rats. Whole body glycolysis rate is measured by estimating the amount of tritiated water accumulated in the blood during 3H-glucose infusion, and whole body glycogen synthesis rate is the difference between whole body glucose turnover rate and whole body glycolysis rate. Calculate by.

6.4.9. Blood, Tissue Collection and Biochemistry At the end of the clamp procedure (9.5 hours fasting), perirenal, retroperitoneal, epididymal and inguinal fat pads and liver weight are recorded. Blood is collected via cardiac puncture and plasma is stored at −80° C. for further assays if necessary (depending on the radioactivity status of the sample). Liver triglyceride content (enzyme colorimetric method) and liver and adipose tissue TNF-α content (enzyme-linked immunosorbent assay (ELISA) method) will be estimated. See US Patent Application Publication No. 2011/0092517, which is incorporated herein by reference in its entirety.

6.5.
[Example 5]
Mouse and rat PPAR transcriptional activation in cell-based transactivation assays 6.5.1. Assay using GAL4-PPAR chimeric receptor 6.5.1.1. Receptor expression plasmid Utilizes the established chimeric receptor system (Lehmann JM et. al. J Biol Chem. 1997; 272(6):3406-10) to allow comparison of relative transcriptional activities of receptor subtypes. Make it. Homo sapiens (hs) (NM _- 006238, NM _- 015869, NM _- 001001928), Rhesus macaque (macacamulatta) (mm) (NM _- 001033029, XM _- 001116676, NM _- 00 1032860), Mus musculus ( m) (NM _- 011144, U10375, NM _- 011146) and mammalian expression vectors pSG5-GAL4-PPARα, pS derived from rattus norvegicus (r) (NM _- 013141, NM _- 013196, NM _- 013124) G5- GAL4-PPARγ and pSG5-GAL4-PPARδ, which are fused to the yeast transcription factor GAL4 DNA-binding domain (amino acids 1-147) and human glucocorticoid receptor (amino acids 1-76), respectively, human PPARα ( For hs and m, amino acids 167-468 and for mm, amino acids 167-467), PPARγ1 (from PPARγ, for hs, amino acids 176-477, for m and mm, amino acids 204-505) and PPARδ ( For hs and mm, express the ligand binding domain (LBD) of amino acids 139-441; for m, amino acids 139-440).

Reporter plasmid: MH100x4-tk-luc (Forman B M et al. Cell. 1995 81(4):541-50) is used as a reporter plasmid.

6.5.1.2. Transient Transfection Assay The African green monkey kidney cell line, CV-1, is used for transfection assays. CV-1 cells are seeded at 0.5×10 ⁵ cells per well in 24-well plates and cultured for 24 hours. The transfection mixture for the chimeric receptor consisted of 30 ng receptor expression plasmid, 120 ng reporter plasmid, 350 ng pCMX-β-galactosidase (βGAL) expression plasmid as a control for transfection efficiency, 250 ng pGEM4 carrier plasmid and Contains 2 μL of lipofection reagent (Lipofectamine2000, Invitrogen). These mixtures are added to the cells and incubated for 5 hours according to the manufacturer's instructions. After transfection, cells are incubated for an additional 40 hours in the presence of an exemplary compound of the invention or each reference compound at various concentrations. Cell lysates are prepared using lysis buffer (passive lysis buffer, Promega) and used for luciferase and βGAL assays. Luciferase and βGAL activities are measured using the Luciferase Assay System (E4030, Promega) and the βGAL Enzyme Assay System (E2000, Promega). Assays are performed in triplicate on GAL4-chimeras. Experiments are repeated at least three times.

6.5.1.3. Calculation of relative PPAR transactivation Each point of relative PPAR transcriptional activity to the maximum activity is calculated based on the following values:

Positive controls as maximal activity (10 ⁻⁵ M GW-590735 for hPPARα, 3×10 ⁻⁵ M rosiglitazone maleate for hPPARγ assay and 10 ⁻⁵ M GW-501516 for hPPARδ) ) and, as the minimum activity, luciferase activity of cells treated with 0.1% DMSO.

6.5.1.4. Calculation of EC ₅₀ Values EC ₅₀ values, defined as the concentration of an exemplary compound of the invention and GW-501516 that produces 50% of maximal reporter activity, are recalculated using Prism software (Graphpad Software).

6.5.1.5. Experiments with 10% serum vs. 0.1% serum Experiments with two serum concentrations: 10% and 0.1%. EC50 is calculated as previously described.

First, we construct this assay and validate the GAL4-chimera/reporter plasmid using Homo sapiens sequences of various PPARs. This experiment is performed with GW501516 (PPARδ agonist) at 10% and 0.1% serum.

Plasmid references are as set forth in US Patent Application Publication No. 2011/0092517, which is incorporated herein by reference in its entirety.

6.6.
[Example 6]
Synthesis of compound IV

アセタール化合物Ｂは、０．１Ｍ ＨＣｌなどの酸触媒の存在下、化合物Ａ（国際公開第２０１１／０２０００１号パンフレット；米国特許第７，２６５，１３７号明細書を参照されたい）およびエチレングリコールから合成する。続いて、化合物Ｂのカルボキシル基をＬｉＡｌＨ_４などの還元試薬を使用してアルコールに還元し、次いで、酸性水で後処理し、これによって、アセタールを除去して、化合物ＩＶを得る。

Acetal compound B is synthesized from compound A (see WO 2011/020001; US Pat. No. 7,265,137) and ethylene glycol in the presence of an acid catalyst such as 0.1 M HCl. do. Subsequently, the carboxyl group of compound B is reduced to an alcohol using a reducing reagent such as LiAlH ₄ and then worked up with acidic water, thereby removing the acetal to yield compound IV.

6.7.
[Example 7]
Synthesis of compounds V, Va and Vb

化合物Ｖは、化合物Ａ（国際公開第２０１１／０２０００１号パンフレット；米国特許第７，２６５，１３７号明細書を参照されたい）から、ＬｉＡｌＨ_４などの還元試薬を使用してカルボン酸およびケトン基を対応するアルコールに還元することによって合成し、化合物Ｖを得る。次に、キラル高速液体クロマトグラフィーを使用して、化合物Ｖを分割して、その（Ｓ）－および（Ｒ）－鏡像異性体を得、各々は、その対応する反対の鏡像異性体を実質的に含まない。

Compound V is obtained by removing the carboxylic acid and ketone groups from compound A (WO 2011/020001; see US Pat. No. 7,265,137) using a reducing reagent such as _LiAlH4 . Compound V is synthesized by reduction to the corresponding alcohol. Compound V is then resolved using chiral high performance liquid chromatography to obtain its (S)- and (R)-enantiomers, each substantially free of its corresponding opposite enantiomer. Not included in

6.8.
[Example 8]
Metabolic profiling of compounds of the invention in cryopreserved hepatocytes 6.8.1. Purpose The purpose of this study was to evaluate the formulas (A) to (H) and (J) to To investigate the formation of metabolites of compounds of the invention, including specific compounds of (AA), Compound IV, Compound V, Compound VI, Compound Va, Compound Vb, Compound VI, Compound VII, and Compound VIII.

6.8.2. Assay Description Compounds of the invention (each a "test article" for purposes of the assay) were incubated in cryopreserved hepatocytes from humans and cynomolgus monkeys, and comparative data regarding stage I and stage II liver metabolites. get.

6.8.2.1. Substances Use the following substances:
CNC-00X
Human hepatocytes, male cynomolgus monkey hepatocytes, male Dulbecco's modified Eagle medium (DMEM)
ITS+1 solution, dexamethasone (Sigma)
Hepatocyte incubation medium (Xenotech)
7-ethoxycoumarin and 7-hydroxycoumarin (Sigma)
Mass spectrometer with LC sample introduction system

6.8.2.2. Procedure Each sample was prepared with 10 μM (diluted from 10 mM DMSO stock solution, 0.2% DMSO in final incubation) of a compound of the invention and cryopreserved hepatocytes (100,000 per well) in a final volume of 100 μL. (final concentration resulting in viable cells). The human hepatocyte incubation buffer is supplemented with DMEM (dexamethasone 3.3 mM; insulin and transferrin, 5 μg/mL each; selenium, 5 ng/mL). Monkey hepatocyte incubation buffer is hepatocyte incubation medium without additional supplements. Incubate the samples at 37° C. in a 96-well plate with gentle shaking in a humidified incubator (95% air/5% CO ₂ ). At T=0, 60 or 120 minutes, the reaction is stopped by adding 100 μL of acetonitrile containing the internal standard (metoprolol). Positive controls, 7-ethoxycoumarin and 7-hydroxycoumarin, are incubated in the same manner as such evaluation compounds.

Samples are centrifuged before analysis by LC-MS using electrospray ionization and SIM monitoring. A positive control, 7-hydroxycoumarin, is assayed using a fluorescent plate reader.

Identification of metabolites is performed until day 5 using LC/MS methods.

Metabolite profiling is based on mass chromatograms of test article-related components.

The LC/MS sensitivity of the metabolites of the test article is assumed to be the same as that of the test article.

6.8.3. Results The compounds of the present invention are found to be metabolized to compounds having PPAR agonist activity and/or metabolites thereof.

7. Particular Embodiment 7.1. Particular Embodiments, Group 1
Various aspects of the present disclosure are described in the numbered embodiments described in the numbered paragraphs below, where references to previous numbered embodiments refer to the previous numbered embodiments in this section 7.1. refers to an embodiment in which
1. Compound of formula (A):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＯＨ、－ＣＯＨ、－ＣＯＯＲ^３、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COOH, -COH, -COOR ³ , -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である）。
２．ラセミ体、または鏡像異性体もしくはジアステレオマーの混合物である、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３．（Ｒ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4).
2. A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is racemic or a mixture of enantiomers or diastereomers.
3. (R)- has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４．（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
4. (S) - has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５．その対応する反対の立体異性体を実質的に含まない、実施形態３もしくは４の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６．（Ｚ）または（Ｅ）のオレフィン異性体の立体配置を有する、実施形態３～５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７．（Ｚ）－異性体であり、構造

A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
5. A compound of embodiment 3 or 4, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding opposite stereoisomer.
6. A compound of any one of Embodiments 3-5, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof, having the olefin isomer configuration of (Z) or (E). drag.
7. (Z) - isomer, structure

を有する、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８．（Ｅ）－異性体であり、構造

A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
8. (E) - isomer, structure

を有する、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９．その対応する他のオレフィン立体配置を実質的に含まない、実施形態７もしくは８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０．（Ｒ）－または（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有する、実施形態７～９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１．Ｒ^１およびＲ^２がそれぞれ、独立して、－Ｃ_１～Ｃ_３アルキルである、実施形態１～１０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２．Ｒ^１およびＲ^２がそれぞれ、独立して、メチルである、実施形態１～１０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３．Ｘが、－ＣＨ_２ＯＨ、－ＣＯＯＨ、－ＣＯＨ、－ＣＯＯＲ^３または－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５である、実施形態１～１２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４．Ｘが、－ＣＨ_２ＯＨまたは－ＣＯＯＨである、実施形態１～１２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５．ｎが０または１である、実施形態１～１４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６．式（Ｂ）の化合物：

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
9. A compound of embodiment 7 or 8, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding other olefinic configuration.
10. A compound of any one of embodiments 7-9, or a pharmaceutically acceptable salt, solvate, ester thereof, having a hydroxyl-containing allylic carbon atom with (R)- or (S)-stereochemistry. , amide or prodrug.
11. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt, solvate thereof, wherein R ¹ and R ² are each independently -C ₁ -C ₃ alkyl; Esters, amides or prodrugs.
12. The compound of any one of embodiments 1-10, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein R ¹ and R ² are each independently methyl. .
13. The compound _of ^any _one of embodiments 1 ^{to 12} , wherein salts, solvates, esters, amides or prodrugs.
14. A compound of any one of embodiments 1-12, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is -CH ₂ OH or -COOH.
15. A compound of any one of embodiments 1-14, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein n is 0 or 1.
16. Compound of formula (B):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１およびＲ^２はそれぞれ、独立して、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルもしくはベンジルであるか、または代替的に、Ｒ^１およびＲ^２は、Ｒ^１およびＲ^２が結合している炭素原子と一緒になって、Ｃ_３～Ｃ_７シクロアルキル基を形成し、
Ｘは、－ＣＨ_２ＯＨ、－ＣＯＨ、－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５、－ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl, or alternatively, R ¹ and R ² together with the carbon atom to which R ¹ and R ² are bonded form a C ₃ -C ₇ cycloalkyl group,
X is -CH ₂ OH, -COH, -COOCH ₂ CONR ⁴ R ⁵ , -SO ₃ H

であり、
Ｒ^３は、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニル、－Ｃ_２～Ｃ_６アルキニル、フェニルまたはベンジルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^４およびＲ^５は、Ｒ^４およびＲ^５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^６およびＲ^７はそれぞれ、独立して、Ｈ、－Ｃ_１～Ｃ_６アルキル、－Ｃ_２～Ｃ_６アルケニルまたは－Ｃ_２～Ｃ_６アルキニルであり、
ｎは、０、１、２、３または４である）。
１７．（Ｚ）－および（Ｅ）－異性体の混合物である、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８．（Ｚ）－異性体であり、構造

and
R ³ is -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl, -C ₂ -C ₆ alkynyl, phenyl or benzyl;
R ⁴ and R ⁵ are each independently alkyl, aryl or heteroaryl, or alternatively, R ⁴ and R ⁵ taken together with the carbon atom to which R ⁴ and R ⁵ are attached to form a heterocycle,
R ⁶ and R ⁷ are each independently H, -C ₁ -C ₆ alkyl, -C ₂ -C ₆ alkenyl or -C ₂ -C ₆ alkynyl;
n is 0, 1, 2, 3 or 4).
17. A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is a mixture of (Z)- and (E)-isomers.
18. (Z) - isomer, structure

を有する、実施形態１６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９．（Ｅ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
19. (E) - isomer, structure

を有する、実施形態１６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０．その対応する他のオレフィン立体配置を実質的に含まない、実施形態１８もしくは１９の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２１．Ｒ^１およびＲ^２がそれぞれ、独立して、－Ｃ_１～Ｃ_３アルキルである、実施形態１６～２０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２２．Ｒ^１およびＲ^２がそれぞれ、独立して、メチルである、実施形態１６～２０のいずれか１つの化合物、または薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２３．Ｘが、－ＣＨ_２ＯＨ、－ＣＯＨまたは－ＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５である、実施形態１６～２２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２４．Ｘが、－ＣＨ_２ＯＨである、実施形態１６～２２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２５．ｎが０または１である、実施形態１６～２４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２６．構造：

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
20. A compound of embodiment 18 or 19, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding other olefinic configuration.
21. The compound of any one of embodiments 16-20, or a pharmaceutically acceptable salt, solvate thereof, wherein R ¹ and R ² are each independently -C ₁ -C ₃ alkyl; Esters, amides or prodrugs.
22. The compound of any one of embodiments 16-20, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug, wherein R ¹ and R ² are each independently methyl.
23. The compound of any one of embodiments 16-22, or a pharmaceutically acceptable salt, solvate, ester thereof, wherein X is -CH ₂ OH, -COH or -COOCH ₂ CONR ⁴ R ⁵ , amide or prodrug.
24. A compound of any one of embodiments 16-22, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is -CH ₂ OH.
25. A compound of any one of embodiments 16-24, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein n is 0 or 1.
26. structure:

を有する化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２７．ラセミ体、または像異性体の混合物である、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２８．（Ｒ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
27. A compound of Embodiment 26, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is racemic or a mixture of optical isomers.
28. (R)- has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２９．（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
29. (S) - has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３０．その対応する反対の鏡像異性体を実質的に含まない、実施形態２８もしくは２９の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３１．（Ｚ）または（Ｅ）のオレフィン異性体の立体配置を有する、実施形態２８～３０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３２．（Ｚ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
30. A compound of embodiment 28 or 29, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding opposite enantiomer.
31. A compound of any one of embodiments 28 to 30, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof, having the olefin isomer configuration of (Z) or (E). drag.
32. (Z) - isomer, structure

を有する、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３３．（Ｅ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
33. (E) - isomer, structure

を有する、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３４．その対応する他のオレフィン立体配置を実質的に含まない、実施形態３２もしくは３３の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３５．（Ｒ）－または（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有する、実施形態３２～３４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３６．構造：

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
34. A compound of embodiment 32 or 33, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding other olefinic configuration.
35. A compound of any one of embodiments 32-34, or a pharmaceutically acceptable salt, solvate, ester thereof, having a hydroxyl-containing allylic carbon atom having (R)- or (S)-stereochemistry. , amide or prodrug.
36. structure:

を有する化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３７．（Ｚ）－および（Ｅ）－異性体の混合物である、実施形態３６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３８．（Ｚ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
37. A compound of embodiment 36, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is a mixture of (Z)- and (E)-isomers.
38. (Z) - isomer, structure

を有する、実施形態３６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３９．（Ｅ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
39. (E) - isomer, structure

を有する、実施形態３６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４０．その対応する他のオレフィン立体配置を実質的に含まない、実施形態３８もしくは３９の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４１．構造：

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
40. A compound of embodiment 38 or 39, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding other olefinic configuration.
41. structure:

を有する化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４２．ラセミ体、または像異性体の混合物である、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４３．（Ｒ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
42. A compound of Embodiment 41, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is racemic or a mixture of optical isomers.
43. (R)- has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４４．（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有し、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
44. (S) - has a hydroxyl-containing allylic carbon atom with stereochemistry and the structure

を有する、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４５．その対応する反対の鏡像異性体を実質的に含まない、実施形態４３もしくは４４の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４６．（Ｚ）または（Ｅ）のオレフィン異性体の立体配置を有する、実施形態４３～４５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４７．（Ｚ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
45. A compound of embodiment 43 or 44, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding opposite enantiomer.
46. A compound of any one of Embodiments 43-45, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof, having the olefin isomer configuration of (Z) or (E). drag.
47. (Z) - isomer, structure

を有する、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４８．（Ｅ）－異性体であり、構造

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
48. (E) - isomer, structure

を有する、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４９．その対応する他のオレフィン立体配置を実質的に含まない、実施形態４７もしくは４８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５０．（Ｒ）－または（Ｓ）－立体化学を有するヒドロキシル含有アリル炭素原子を有する、実施形態４７～４９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５１．有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、およびビヒクルの薬学的に許容される担体を含む、組成物。
５２．別の治療活性剤をさらに含む、実施形態５１の組成物。
５３．他の治療活性剤が、脂質低下薬、スタチン、コレステロール吸収阻害剤、ＰＣＳＫ９に対する抗体、ｓｉＲＮＡ ＰＣＳＫ９、抗線維化剤、甲状腺ホルモン、選択的甲状腺受容体－βアゴニスト、アポトーシスシグナル調節性キナーゼ１（ＡＳＫ１）阻害剤、アセチル－ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害剤、インテグリンアンタゴニストまたは非ステロイド系ファルネソイドＸ受容体（ＦＸＲ）アゴニストである、実施形態５２の組成物。
５４．脂質低下薬が、ゲムフィブロジル、フェノフィブレート、ベザフィブレート、クロフィブレート、シプロフィブレート、クリノフィブラート、エトフィリン、ピリフィブラート、シムフィブラート、トコフィブラートまたはペマフィブラートである、
スタチンが、アトルバスタチン、シンバスタチン、プラバスタチン、ロスバスタチン、フルバスタチン、ロバスタチン、ピタバスタチン、メバスタチン、ダルバスタチン、ジヒドロコンパクチンもしくはセリバスタチン、または薬学的に許容されるそれらの塩、溶媒和物、エステル、アミドもしくはプロドラッグである、
コレステロール吸収阻害剤が、エゼチミブである、
ＰＣＳＫ９に対する抗体が、エボロクマブ アルイロクマブ、ボコシズマブ、１Ｄ０５－ＩｇＧ２、ＲＧ７６５２、ＬＹ３０１５０１４またはＬＧＴ－２０９である、
ｓｉＲＮＡ ＰＣＳＫ９が、インクリシランであり、
抗線維化剤が、ニタゾキサミド、チゾキサニドもしくはチゾキサニドグルクロニド、または薬学的に許容されるそれらの塩、溶媒和物、エステル、アミドもしくはプロドラッグである、
選択的甲状腺受容体－βアゴニストが、ＶＫ２８０９、ＭＧＬ－３１９６、ＭＧＬ－３７４５、ＳＫＬ－１４７６３、ソベチロメ、ＢＣＴ３０４、ＺＹＴ１、ＭＢ－０７８１またはエプロチロームである、
ＡＳＫ１阻害剤が、セロンセルチブである、
ＡＣＣ阻害剤が、フィルソコスタットである、
インテグリンアンタゴニストが、α５β１阻害剤または汎インテグリン阻害剤である、または
ＦＸＲアゴニストが、シロフェクソルである、
実施形態５３の化合物。
５５．肝臓障害、脂質代謝異常、異常リポタンパク血症、腎疾患、グルコース代謝の障害、脂質代謝の障害、糖質代謝の障害、心血管疾患、血管疾患、メタボリックシンドローム、メタボリックシンドロームに伴う合併症、ＰＰＡＲ関連障害、敗血症、血栓障害、肥満、糖尿病性腎症、糖尿病性網膜症、アテローム性動脈硬化、膵臓炎、脳血管疾患、血管新生に関連する障害、高血圧、がん、炎症、炎症性疾患、神経変性疾患、自己免疫疾患、腫瘍性疾患、筋萎縮、胆汁鬱滞、ミトコンドリアの機能不全、眼疾患、リソソーム蓄積症、腎臓病もしくは勃起不全を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
５６．肝臓障害が、肝臓細胞の病理的な破壊、炎症、変性、アポトーシスまたは増殖を含む、実施形態５５の方法。
５７．肝臓障害が、肝線維症、脂肪肝疾患、非アルコール性脂肪性肝疾患（ＮＡＦＬＤ）または非アルコール性脂肪性肝炎（ＮＡＳＨ）である、実施形態５５の方法。
５８．脂質代謝異常が、高脂血症であること、または対象の血漿もしくは血清中の高密度リポタンパク質コレステロール（ＨＤＬ－Ｃ）の濃度が異常に低いことである、実施形態５５の方法。
５９．高脂血症が、高コレステロール血症、家族性高コレステロール血症、高トリグリセリド血症または家族性複合型高脂血症である、実施形態５８の方法。
６０．高脂血症が、対象の血漿もしくは血清中のリポタンパク質リパーゼレベルまたは活性の異常低下または不足、あるいは対象の血漿もしくは血清中のケトン体、リポタンパク質（ａ）コレステロール（Ｌｐ（ａ）－Ｃ）、低密度リポタンパク質（ＬＤＬ）、超低密度リポタンパク質コレステロール（ＶＬＤＬ－Ｃ）または非エステル化脂肪酸の異常に高い濃度を特徴とする、実施形態５８の方法。
６１．リポタンパク質リパーゼレベルもしくは活性の低下または不足が、リポタンパク質リパーゼをコードする遺伝子の変異の結果である、実施形態６０の方法。
６２．異常リポタンパク血症が、対象の血漿または血清中の異常に高い濃度のＬＤＬ、アポリポタンパク質（ａ）もしくはＶＬＤＬ、または対象の血漿または血清中の異常に低い濃度の高密度リポタンパク質（ＨＤＬ）もしくはリポタンパク質リパーゼを特徴とする、実施形態５５の方法。
６３．リポタンパク質リパーゼの濃度が異常に低いことが、リポタンパク質リパーゼ変異、低アルファリポタンパク血症、糖尿病に伴うリポタンパク質異常、肥満に伴うリポタンパク質異常、アルツハイマー病に伴うリポタンパク質異常または家族性複合型高脂血症に関連する、実施形態６２の方法。
６４．腎疾患が、糸球体疾患、細管疾患、尿細管間質疾患、急性または急速進行性の腎不全、慢性腎不全、腎結石または腫瘍である、実施形態５５の方法。
６５．糸球体疾患が、急性糸球体腎炎、慢性糸球体腎炎、迅速進行性糸球体腎炎、ネフローゼ症候群、限局性増殖性糸球体腎炎、全身性疾患に伴う糸球体病変、グッドパスチャー症候群、多発性骨髄腫、糖尿病、新生物形成、鎌状赤血球症または慢性炎症性疾患である、
細管疾患が、急性尿細管壊死、急性腎不全、多発性嚢胞腎疾患、髄質海綿腎、髄質嚢胞性疾患、腎性糖尿病または腎尿細管アシドーシスである、
尿細管間質疾患が、腎盂腎炎、薬物もしくは毒素誘発性尿細管間質性腎炎、高カルシウム腎症または低カリウム性腎症である、または
腫瘍が、腎細胞癌または腎芽腫である、
実施形態６４の方法。
６６．全身性疾患に伴う糸球体病変が、全身性エリテマトーデスである、実施形態６５の方法。
６７．腎疾患が、高血圧、腎硬化症、微小血管障害性溶血性貧血、アテローム塞栓性腎疾患、びまん性皮質壊死または腎塞栓である、実施形態５５の方法。
６８．高血圧が、本態性高血圧、高血圧、高血圧、悪性高血圧、二次性高血圧または白衣高血圧である、実施形態６７の方法。
６９．グルコース代謝の障害が、耐糖能異常；インスリン抵抗性；インスリン抵抗性関連乳がん、結腸または前立腺がん；糖尿病；膵臓炎；高血圧；多嚢胞性卵巣疾患；あるいは対象の血漿もしくは血清における異常に高い濃度の血中インスリンまたはグルコースである、実施形態５５の方法。
７０．糖尿病が、非インスリン依存性糖尿病（ＮＩＤＤＭ）、インスリン依存性糖尿病（ＩＤＤＭ）、妊娠糖尿病（ＧＤＭ）または若年発症成人型糖尿病（ＭＯＤＹ）である、実施形態６９の方法。
７１．血管疾患または心血管疾患が、末梢血管疾患、冠状動脈性心疾患、脳卒中、再狭窄、動脈硬化、虚血、内皮機能不全、虚血－再灌流損傷、心筋梗塞または脳梗塞である、実施形態５５の方法。
７２．ＰＰＡＲ関連障害が、関節リウマチ、多発性硬化症、乾癬、炎症性腸疾患、乳がん、結腸がんまたは前立腺がんである、実施形態５５の方法。
７３．ＰＰＡＲ関連障害が、血管疾患、筋疾患、脱髄疾患、筋肉構造障害、神経活性化障害、筋肉疲労障害、筋肉量障害、ミトコンドリア疾患、ミトコンドリアの機能不全、ベータ酸化疾患または代謝性疾患である、実施形態５５の方法。
７４．筋疾患が、筋ジストロフィー疾患である、
脱髄疾患が、多発性硬化症、シャルコー－マリー－トゥース病、ペリツェウス－メルツバッハー病、脳脊髄炎、視神経脊髄炎、副腎白質ジストロフィーまたはギランバレー症候群である、
筋肉構造障害が、ベスレムミオパチー、セントラルコア病、先天性筋線維不均等症、遠位筋ジストロフィー（ＭＤ）、デュシェンヌ型およびベッカー型ＭＤ、エメリー－ドレイフス型ＭＤ、顔面肩甲上腕型ＭＤ、ヒアリン体ミオパチー、肢帯型ＭＤ、筋ナトリウムチャネル障害、筋緊張性軟骨形成異常、筋強直性ジストロフィー、筋細管ミオパチー、ネマリン小体疾患、眼咽頭型ＭＤまたは腹圧性尿失禁である、
神経活性化障害が、筋萎縮性側索硬化症、シャルコー－マリー－トゥース病、ギラン－バレー症候群、ランバート－イートン症候群、多発性硬化症、重症筋無力症、神経病変、末梢神経障害、脊髄性筋萎縮症、遅発性尺骨神経麻痺または毒性筋神経障害である、
筋肉疲労障害が、慢性疲労症候群、糖尿病（Ｉ型またはＩＩ型）、糖原病、線維筋痛症、フリードライヒ運動失調症、間欠性跛行、脂質蓄積性ミオパチー、ＭＥＬＡＳ（ミトコンドリア脳症、乳酸アシド－シスおよび脳卒中様エピソード）症候群、ムコ多糖症、ポンペ病または甲状腺中毒性ミオパチーである、
筋肉量障害が、悪液質、軟骨退化、脳性麻痺、コンパートメント症候群、重症疾患ミオパチー、封入体筋炎、筋萎縮症（廃用性）、サルコペニア、ステロイドミオパチーまたは全身性エリテマトーデスである、
ミトコンドリア疾患が、アルパーズ疾患、慢性進行性外眼筋麻痺（ＣＰＥＯ）、カーンズ－セイラ症候群（ＫＳＳ）、レーベル遺伝性視神経障害（ＬＨＯＮ）、ＭＥＬＡＳ、ミオクロニーてんかんおよび赤色ぼろ線維疾患（ＭＥＲＲＦ）、神経原性筋力低下（ＮＡＲＰ）、運動失調症、網膜色素変性、ピアソン症候群、ミトコンドリアの機能不全またはミトコンドリアの機能喪失である、
ベータ酸化疾患が、全身性カルニチン輸送体、カルニチンパルミトイルトランスフェラーゼ（ＣＰＴ）ＩＩ欠損症、極長鎖アシル－ＣｏＡデヒドロゲナーゼ（ＬＣＨＡＤまたはＶＬＣＡＤ）欠損症、三頭酵素欠損症、中鎖アシル－ＣｏＡデヒドロゲナーゼ（ＭＣＡＤ）欠損症、短鎖アシル－ＣｏＡデヒドロゲナーゼ（ＳＣＡＤ）欠損症またはβ－酸化のリボフラビン応答性障害（ＲＲ－ＭＡＤＤ）である、または
代謝性疾患が、高脂血症、脂質代謝異常、高コレステロール血症、高トリグリセリド血症、ＨＤＬ低コレステロール血症、ＬＤＬ高コレステロール血症、ＨＬＤ非コレステロール血症、ＶＬＤＬ高タンパク血症、異常リポタンパク血症、アポリポタンパク質Ａ－Ｉ低タンパク血症、アテローム性動脈硬化、動脈硬化の疾患、心血管系の疾患、脳血管疾患、末梢循環器系疾患、メタボリックシンドローム、症候群Ｘ、肥満、糖尿病、Ｉ型糖尿病、ＩＩ型糖尿病、高血糖症、インスリン抵抗性、耐糖能異常、高インスリン症、糖尿病合併症、心不全、心筋梗塞、心筋症、高血圧、非アルコール性脂肪性肝疾患（ＮＡＦＬＤ）、非アルコール性脂肪性肝炎（ＮＡＳＨ）、血栓、アルツハイマー病、神経変性疾患、脱髄疾患、多発性硬化症、副腎白質ジストロフィー、皮膚炎、乾癬、ざ瘡、皮膚老化、多毛症、炎症、関節炎、喘息、過敏性腸症候群、潰瘍性大腸炎、クローン病または膵臓炎である、
実施形態７３の方法。
７５．筋ジストロフィー疾患が、デュシェンヌ型筋ジストロフィー、ベッカー型筋ジストロフィー、肢帯型筋ジストロフィー、先天性筋ジストロフィー、顔面肩甲上腕型筋ジストロフィー、筋強直性ジストロフィー、眼咽頭型筋ジストロフィー、遠位筋ジストロフィーまたはエメリー－ドレフュス型筋ジストロフィーである、実施形態７４の方法。
７６．ＰＰＡＲ関連障害が、対象の血漿または血清中の、異常に低い濃度のＨＤＬ、異常に低い濃度のアポリポタンパク質Ａ－Ｉ（アポＡ－Ｉ）、異常に高い濃度のＶＬＤＬ－Ｃ、異常に高い濃度の低密度リポタンパク質コレステロール（ＬＤＬ－Ｃ）、異常に高い濃度のトリグリセリド、異常に高い濃度のアポリポタンパク質Ｂ（アポＢ）、異常に高い濃度のアポリポタンパク質Ｃ－ＩＩＩ（アポＣ－ＩＩＩ）またはリポタンパク質リパーゼ活性に対するヘパリン投与後の肝リパーゼの異常に低い比である、実施形態５５の方法。
７７．ＰＰＡＲ関連障害が、対象のリンパ液または脳脊髄液中の異常に高い濃度のＨＤＬまたは異常に低濃度のアポＡ－Ｉである、実施形態５５の方法。
７８．肥満が腹部肥満である、実施形態５５の方法。
７９．脳血管疾患が脳虚血である、実施形態５５の方法。
８０．血管新生に関連する障害が、網膜症または糖尿病である、実施形態５５の方法。
８１．がんが、ヒト肉腫またはヒト癌である、実施形態５５の方法。
８２．がんが、線維肉腫、粘液肉腫、脂肪肉腫、軟骨肉腫、骨原性肉種、脊索腫、血管肉腫、内皮肉腫、リンパ管肉腫、リンパ管内皮肉腫、滑膜腫、中皮腫、ユーイング腫瘍、平滑筋肉腫、横紋筋肉腫、結腸癌、膵臓がん、骨がん、乳がん、卵巣がん、前立腺がん、食道がん、口内がん、鼻腔がん、扁平上皮癌、基底細胞癌、腺癌、汗腺癌、脂腺癌、乳頭状癌、乳頭腺癌、嚢胞腺癌、髄様癌、気管支原性癌、腎細胞癌、肝細胞腫、胆管癌、絨毛癌、精上皮腫、胎生期癌、ウィルムス腫瘍、子宮頚がん、子宮がん、睾丸腫瘍、肺癌、小細胞肺癌、膀胱癌、上皮性癌、神経膠腫、星状細胞腫、髄芽腫、頭蓋咽頭腫、上衣腫、松果体腫、血管芽腫、聴神経鞘腫、乏突起神経膠腫、髄膜腫、皮膚がん、黒色腫、神経芽細胞腫、網膜芽細胞腫、白血病、急性Ｂ細胞リンパ芽球性白血病、急性Ｔ細胞リンパ芽球性白血病、急性前骨髄球性白血病、急性単芽球性白血病、急性赤白血病性白血病、急性巨核芽球性白血病、急性骨髄単球性白血病、急性非リンパ性白血病、急性未分化白血病、慢性骨髄性白血病、有毛細胞白血病、リンパ芽球性白血病、骨髄性白血病、リンパ性白血病、骨髄性白血病、真性多血症、多発性骨髄腫、リンパ腫、ホジキン病、非ホジキンリンパ腫、ワルデンシュトレームマクログロブリン血症または重鎖病である、実施形態５５の方法。
８３．白血病が、急性または慢性リンパ芽球性白血病、骨髄性白血病、リンパ性白血病、リンパ性白血病または骨髄性白血病である、実施形態８２の方法。
８４．骨髄性白血病が、急性であり、骨髄芽球性白血病、前骨髄球性白血病、骨髄単球性白血病、単球性白血病または赤白血病である、実施形態８３の方法。
８５．リンパ腫が、ホジキンリンパ腫または非ホジキンリンパ腫である、実施形態８３の方法。
８６．炎症性疾患が、多発性硬化症、関節の慢性炎症性障害、関節炎、呼吸窮迫症候群、炎症性腸疾患、炎症性肺障害、炎症性障害、歯肉の炎症性障害、結核、ハンセン病、腎臓の炎症性疾患、皮膚の炎症性障害、中枢神経系の炎症性疾患、全身性エリテマトーデス（ＳＬＥ）または心臓の炎症性疾患である、実施形態５５の方法。
８７．関節炎が、関節リウマチまたは骨関節炎である、
炎症性腸疾患が、回腸炎、潰瘍性大腸炎またはクローン病である、
炎症性肺障害が、喘息または慢性閉塞性気道疾患である、
眼の炎症性障害が、角膜ジストロフィー、トラコーマ、オンコセルカ症、ぶどう膜炎、交感性眼炎または眼内炎である、
歯肉の炎症性障害が、歯周炎または歯ぎん炎である、
腎臓の炎症性疾患が、糸球体腎炎またはネフローゼである、
皮膚の炎症性障害が、ざ瘡、硬化性皮膚炎、乾癬、湿疹、光老化またはしわである、
中枢神経系の炎症性疾患が、ＡＩＤＳ関連神経変性、脳卒中、神経外傷、アルツハイマー病、脳脊髄炎またはウイルス性もしくは自己免疫性脳炎である、または
心臓の炎症性疾患が、心筋症である、
実施形態８６の方法。
８８．神経変性疾患が、アルツハイマー病またはハンチントン病である、実施形態５５の方法。
８９．自己免疫疾患が、免疫複合性血管炎、全身性ループスまたはエリトマトーデスである、実施形態５５の方法。
９０．腫瘍性疾患が発がんである、実施形態５５の方法。
９１．胆汁鬱滞が、肝内胆汁鬱滞性疾患または肝外胆汁鬱滞性疾患である、実施形態５５の方法。
９２．肝内胆汁鬱滞性疾患が、原発性胆汁性胆管炎（ＰＢＣ）、原発性硬化性胆管炎（ＰＳＣ）、進行性家族性肝内胆汁鬱滞症（ＰＦＩＣ）またはアラジール症候群（ＡＳ）である、実施形態９１の方法。
９３．眼疾患が、ドライアイ、マイボーム腺機能不全、角結膜上皮障害、角膜上皮障害または角膜潰瘍である、実施形態５５の方法。
９４．リソソーム貯蔵障害が、神経セロイドリポフスチン症、アルツハイマー病、ハンチントン病、筋萎縮性脊髄側索硬化症（ＡＬＳ）、パーキンソン病、多系統萎縮症（ＭＳＡ）、進行性核上麻痺（ＰＳＰ）、大脳皮質基底核変性症（ＣＢＤ）、レビー小体による認知症（ＤＬＢ）、オートファジー経路の障害、ティーサックス病、ファブリー病、ニーマンピック病、ゴーシェ病、ハンター症候群、アルファ－マンノシドーシス、アスパルチルグルコサミン尿症、コレステロールエステル貯蔵病、慢性ヘキソサミニダーゼＡ欠損症、シスチン症、ダノン病、ファーバー病、フコイドーシス、ガラクトシアリドーシスまたはバッテン病である、実施形態５５の方法。
９５．腎臓病が、腎虚血再灌流損傷である、実施形態５５の方法。
９６．勃起不全が、神経、動脈、平滑筋もしくは線維組織への損傷；糖尿病；腎臓病；アルコール依存症；多発性硬化症；アテローム性動脈硬化；血管疾患；または神経学的疾患に起因する、実施形態５５の方法。
９７．脂質異常症、高脂血症、高リポタンパク血症、高コレステロール血症、高トリグリセリド血症もしくは脂質代謝異常を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
９８．高コレステロール血症が、ホモ接合性家族性高コレステロール血症である、実施形態９７の方法。
９９．対象の血漿または血清において、異常に高い濃度の高低密度リポタンパク質（ＬＤＬ）、アポリポタンパク質Ｂ（アポＢ）、リポタンパク質（ａ）（Ｌｐ（ａ））、アポリポタンパク質（ａ）、もしくは超低密度リポタンパク質（ＶＬＤＬ）を有する対象を処置する、または対象が異常に高い濃度の上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１００．対象の血漿または血清において、異常に低い濃度の高密度リポタンパク質（ＨＤＬ）を有する対象を処置する、または対象が異常に低い濃度の上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０１．対象の血漿または血清において、リポタンパク質リパーゼ濃度もしくは活性の異常低下または不足を有する対象を処置する、または対象が上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０２．リポタンパク質リパーゼレベルもしくは活性の低下または不足が、リポタンパク質リパーゼをコードする遺伝子の変異の結果である、実施形態１０１の方法。
１０３．低アルファリポタンパク血症、糖尿病に伴うリポタンパク質異常、肥満に伴うリポタンパク質異常、アルツハイマー病に関連するリポタンパク質異常もしくは家族性複合型高脂血症を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０４．対象の血漿または血清中の、異常に高い濃度のトリグリセリド、低密度リポタンパク質コレステロール（ＬＤＬ－Ｃ）、超低密度リポタンパク質コレステロール（ＶＬＤＬ－Ｃ）、非高密度リポタンパク質コレステロール（非ＨＤＬ－Ｃ）、リポタンパク質（ａ）（Ｌｐ（ａ））、アポリポタンパク質Ｂ、ＨＤＬ／（ＶＬＤＬ＋ＬＤＬ）比、アポリポタンパク質Ｃ－ＩＩまたはアポリポタンパク質Ｃ－ＩＩＩを低下させる方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０５．対象の血漿または血清中の、高密度リポタンパク質（ＨＤＬ）関連タンパク質、ＨＤＬ－コレステロール、アポリポタンパク質Ａ－Ｉまたはアポリポタンパク質Ｅの異常に低い濃度を向上させる方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０６．ＨＤＬ関連タンパク質が、アポリポタンパク質Ａ－Ｉ（アポＡ－Ｉ）、アポリポタンパク質Ａ－ＩＩ（アポＡ－ＩＩ）、アポリポタンパク質Ａ－ＩＶ（アポＡ－ＩＶ）またはアポリポタンパク質Ｅ（アポＥ）である、実施形態１０５の方法。
１０７．対象の血漿または血清に由来するトリグリセリドのクリアランスを促進する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０８．対象における、異常に低いグルコース代謝または脂質代謝を向上させる方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１０９．異常に低いグルコース代謝を向上させる方法により、対象のインスリン感度または酸素消費が増大するか、あるいは対象の血漿または血清における血中インスリン、血糖もしくは糖化ヘモグロビンが低下する、実施形態１０８の方法。
１１０．異常に低い脂質代謝を向上させる方法が、対象の血漿もしくは血清における、ＬＤＬまたは遊離トリグリセリドの濃度を低下させるか、またはけん化されたもしくはけん化されていない脂肪酸合成を阻害する、実施形態１０８の方法。
１１１．炎症、全身性エリテマトーデス、ループス腎炎もしくは関節炎から選択される疾患の症状を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１１２．関節炎が、アジュバント関節炎またはＩＩ型コラーゲン誘発性関節炎である、実施形態１１１の方法。
１１３．症状が、腎炎、腎不全または腎機能低下である、実施形態１１１の方法。
１１４．家畜における肉の脂肪含有率を低下させる方法であって、家畜に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１１５．家禽卵のコレステロール含有率を低下させる方法であって、家禽の種に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１１６．急性腎臓損傷（ＡＫＩ）を有するか、またはＡＫＩのリスクにある対象を処置する方法であって、対象に、有効量の実施形態１～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
１１７．化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグが静脈内に投与される、実施形態１１６の方法であって、場合により、必要に応じて３日間、１日１回、静脈内投与するステップを含む、方法。
１１８．化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグが経口投与される、実施形態１１６の方法。
１１９．ＡＫＩが、敗血症に関係するＡＫＩである、実施形態１１６～１１８のいずれか１つの方法。
１２０．ＡＫＩが、虚血／再灌流ＡＫＩである、実施形態１１６～１１８のいずれか１つの方法。
１２１．ＡＫＩが、急性間質性腎炎に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２２．ＡＫＩが、糸球体腎疾患に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２３．ＡＫＩが、血管炎性腎疾患に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２４．ＡＫＩが、虚血に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２５．ＡＫＩが、毒性傷害に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２６．ＡＫＩが、前腎性高窒素血症に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２７．ＡＫＩが、急性腎後性閉塞性（destructive）腎障害に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２８．ＡＫＩが、糖尿病に起因する、実施形態１１６～１１８のいずれか１つの方法。
１２９．ＡＫＩが、根本的な腎不全に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３０．ＡＫＩが、腎炎症候群に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３１．ＡＫＩが、アテローム性動脈硬化疾患に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３２．ＡＫＩが、低血圧に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３３．ＡＫＩが、低酸素症に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３４．ＡＫＩが、ミオグロビン尿症－血尿に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３５．ＡＫＩが、肝疾患に起因する、実施形態１１６～１１８のいずれか１つの方法。
１３６．ＡＫＩが、ウイルス感染に続発し、場合により、ウイルス感染がＣＯＶＩＤ－１９である、実施形態１１６～１１８のいずれか１つの方法。
１３７．対象がウイルス感染を有しており、場合により、ウイルス感染がＣＯＶＩＤ－１９である、実施形態１３６の方法。
１３８．対象が敗血症を有する、１１６～１１９の方法。
１３９．敗血症がグラム陰性菌感染に伴う、実施形態１３７の方法。
１４０．対象が腹腔内腔感染を有する、実施形態１３８または実施形態１３９の方法。
１４１．対象が尿性敗血症を有する、実施形態１３８または実施形態１３９の方法。
１４２．対象が老年者である、実施形態１１６～１４１のいずれか１つの方法。
１４３．対象が手術患者である、実施形態１１６～１４２のいずれか１つの方法。
１４４．手術患者が、心臓血管手術を受け、場合により、この手術が、冠状動脈バイパス移植（ＣＡＢＧ）手術および／または心臓弁手術である、実施形態１４３の方法。
１４５．対象が妊婦である、実施形態１１６～１４１のいずれか１つの方法。
１４６．対象が腎毒性剤に曝露されてきた、実施形態１１６～１４５のいずれか１つの方法。
１４７．腎毒性剤が、シスプラチン、ゲンタマイシン、セファロリジン、シクロスポリン、アンホテリシン、四塩化炭素、トリクロロエチレン、ジクロロアセチレンまたはそれらの組合せを含む、実施形態１４６の方法。
１４８．対象がＡＫＩを有する、実施形態１１６～１４７のいずれか１つの方法。
１４９．有効量が、ＡＫＩの重症度を低下させるのに有効である、実施形態１４８の方法。
１５０．対象がＡＫＩのリスクにある、実施形態１１６～１４７のいずれか１つの方法。
１５１．対象が、場合により、冠状動脈バイパス移植（ＣＡＢＧ）手術および／または心臓弁手術である心臓血管手術の後に、ＡＫＩのリスクにある、実施形態１１６～１４７のいずれか１つの方法。
１５２．有効量が、対象がＡＫＩを発症する可能性を低減するのに有効な、実施形態１５０または実施形態１５１の方法。
１５３．有効量が、ＡＫＩの発生を遅延させるのに有効な、実施形態１５０～１５２のいずれか１つの方法。
１５４．有効量が、ＡＫＩを予防するのに有効な、実施形態１５０～１５２のいずれか１つの方法。
１５５．対象がＡＫＩを発症する場合、有効量は、ＡＫＩの重症度を低下させるのに有効な、実施形態１５０～１５２のいずれか１つの方法。
１５６．対象が、化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、あるいは医薬組成物を投与する前に、１～４のＳＯＦＡスコアを有する、実施形態１１６～１５５のいずれか１つの方法。
１５７．対象が、投与前に２～４のＳＯＦＡスコアを有する、実施形態１５６の方法。
１５８．対象が、投与前に１のＳＯＦＡスコアを有する、実施形態１５６の方法。
１５９．対象が、投与前に２のＳＯＦＡスコアを有する、実施形態１５６の方法。
１６０．対象が、投与前に３のＳＯＦＡスコアを有する、実施形態１５６の方法。
１６１．対象が、投与前に４のＳＯＦＡスコアを有する、実施形態１５６の方法。
１６２．対象が、投与前に、＞０．６の内毒素活性レベルを有する、実施形態１１６～１６１のいずれか１つの方法。
１６３．有効量が、対象の内毒素活性レベルを低下させるのに有効な、実施形態１１６～１６２のいずれか１つの方法。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
49. A compound of embodiment 47 or 48, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, substantially free of its corresponding other olefinic configuration.
50. The compound of any one of embodiments 47-49, or a pharmaceutically acceptable salt, solvate, ester thereof, having a hydroxyl-containing allylic carbon atom with (R)- or (S)-stereochemistry , amide or prodrug.
51. an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, and a pharmaceutically acceptable carrier of the vehicle. ,Composition.
52. The composition of embodiment 51 further comprising another therapeutically active agent.
53. Other therapeutically active agents include lipid-lowering drugs, statins, cholesterol absorption inhibitors, antibodies against PCSK9, siRNA PCSK9, antifibrotic agents, thyroid hormones, selective thyroid receptor-β agonists, apoptosis signal-regulated kinase 1 (ASK1 53.) The composition of embodiment 52 is an acetyl-CoA carboxylase (ACC) inhibitor, an integrin antagonist, or a non-steroidal farnesoid X receptor (FXR) agonist.
54. the lipid-lowering drug is gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate, clinofibrate, etofylline, pyrifibrate, simfibrate, tocofibrate or pemafibrate,
the statin is atorvastatin, simvastatin, pravastatin, rosuvastatin, fluvastatin, lovastatin, pitavastatin, mevastatin, dalvastatin, dihydrocompactin or cerivastatin, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof; be,
the cholesterol absorption inhibitor is ezetimibe,
The antibody against PCSK9 is evolocumab, alirocumab, bococizumab, 1D05-IgG2, RG7652, LY3015014 or LGT-209,
siRNA PCSK9 is inclisiran,
the antifibrotic agent is nitazoxamide, tizoxanide or tizoxanide glucuronide, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof;
the selective thyroid receptor-β agonist is VK2809, MGL-3196, MGL-3745, SKL-14763, sobetylome, BCT304, ZYT1, MB-0781 or eprotylome;
the ASK1 inhibitor is selonsertib,
the ACC inhibitor is filsocostat,
The integrin antagonist is an α5β1 inhibitor or a pan-integrin inhibitor, or the FXR agonist is Cilofexor.
Compounds of Embodiment 53.
55. Liver disorder, lipid metabolism disorder, dyslipoproteinemia, renal disease, glucose metabolism disorder, lipid metabolism disorder, carbohydrate metabolism disorder, cardiovascular disease, vascular disease, metabolic syndrome, complications associated with metabolic syndrome, PPAR Related disorders, sepsis, thrombotic disorders, obesity, diabetic nephropathy, diabetic retinopathy, atherosclerosis, pancreatitis, cerebrovascular diseases, disorders related to angiogenesis, hypertension, cancer, inflammation, inflammatory diseases, A method of treating or preventing neurodegenerative disease, autoimmune disease, oncological disease, muscle atrophy, cholestasis, mitochondrial dysfunction, eye disease, lysosomal storage disease, kidney disease or erectile dysfunction, requiring the same. A method comprising administering to a subject an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
56. 56. The method of embodiment 55, wherein the liver injury comprises pathological destruction, inflammation, degeneration, apoptosis or proliferation of liver cells.
57. 56. The method of embodiment 55, wherein the liver disorder is liver fibrosis, fatty liver disease, nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH).
58. 56. The method of embodiment 55, wherein the lipid metabolism disorder is hyperlipidemia or an abnormally low concentration of high-density lipoprotein cholesterol (HDL-C) in the plasma or serum of the subject.
59. 59. The method of embodiment 58, wherein the hyperlipidemia is hypercholesterolemia, familial hypercholesterolemia, hypertriglyceridemia, or familial combined hyperlipidemia.
60. Hyperlipidemia is an abnormal decrease or deficiency in lipoprotein lipase levels or activity in the subject's plasma or serum, or ketone bodies, lipoprotein (a) cholesterol (Lp(a)-C) in the subject's plasma or serum. 59. The method of embodiment 58, characterized by an abnormally high concentration of low density lipoprotein (LDL), very low density lipoprotein cholesterol (VLDL-C), or non-esterified fatty acids.
61. 61. The method of embodiment 60, wherein the reduced or deficient lipoprotein lipase level or activity is the result of a mutation in the gene encoding lipoprotein lipase.
62. Dyslipoproteinemia is characterized by an abnormally high concentration of LDL, apolipoprotein (a), or VLDL in the subject's plasma or serum, or an abnormally low concentration of high-density lipoprotein (HDL) or 56. The method of embodiment 55, characterized by lipoprotein lipase.
63. Abnormally low levels of lipoprotein lipase can be caused by lipoprotein lipase mutations, hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial complex. 63. The method of embodiment 62, relating to hyperlipidemia.
64. 56. The method of embodiment 55, wherein the renal disease is glomerular disease, tubular disease, tubulointerstitial disease, acute or rapidly progressive renal failure, chronic renal failure, renal stone or tumor.
65. Glomerular disease is acute glomerulonephritis, chronic glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, focal proliferative glomerulonephritis, glomerular lesions associated with systemic disease, Goodpasture syndrome, multiple myeloma , diabetes, neoplasia, sickle cell disease or chronic inflammatory disease;
the tubular disease is acute tubular necrosis, acute renal failure, polycystic kidney disease, medullary cavernous kidney, medullary cystic disease, renal diabetes mellitus or renal tubular acidosis;
The tubulointerstitial disease is pyelonephritis, drug- or toxin-induced tubulointerstitial nephritis, hypercalcemic or hypokalemic nephropathy, or the tumor is renal cell carcinoma or nephroblastoma.
The method of embodiment 64.
66. 66. The method of embodiment 65, wherein the glomerular lesion associated with a systemic disease is systemic lupus erythematosus.
67. 56. The method of embodiment 55, wherein the renal disease is hypertension, nephrosclerosis, microangiopathic hemolytic anemia, atheroembolic renal disease, diffuse cortical necrosis, or renal embolism.
68. 68. The method of embodiment 67, wherein the hypertension is essential hypertension, hypertension, hypertension, malignant hypertension, secondary hypertension or white coat hypertension.
69. Disorders of glucose metabolism may result in glucose intolerance; insulin resistance; insulin resistance-related breast, colon, or prostate cancer; diabetes; pancreatitis; hypertension; polycystic ovary disease; or abnormally high concentrations in the subject's plasma or serum. 56. The method of embodiment 55, wherein the blood insulin or glucose.
70. 70. The method of embodiment 69, wherein the diabetes is non-insulin dependent diabetes mellitus (NIDDM), insulin dependent diabetes mellitus (IDDM), gestational diabetes mellitus (GDM) or young onset adult diabetes mellitus (MODY).
71. Embodiments where the vascular disease or cardiovascular disease is peripheral vascular disease, coronary heart disease, stroke, restenosis, arteriosclerosis, ischemia, endothelial dysfunction, ischemia-reperfusion injury, myocardial infarction or cerebral infarction. 55 methods.
72. 56. The method of embodiment 55, wherein the PPAR-associated disorder is rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, breast cancer, colon cancer, or prostate cancer.
73. The PPAR-related disorder is a vascular disease, a muscle disease, a demyelinating disease, a muscle structure disorder, a neural activation disorder, a muscle fatigue disorder, a muscle mass disorder, a mitochondrial disease, a mitochondrial dysfunction, a beta oxidation disease or a metabolic disease, The method of embodiment 55.
74. The muscle disease is muscular dystrophy disease,
the demyelinating disease is multiple sclerosis, Charcot-Marie-Tooth disease, Pelizaus-Merzbacher disease, encephalomyelitis, neuromyelitis optica, adrenoleukodystrophy or Guillain-Barre syndrome;
Muscle structural disorders include Bethlem myopathy, central core disease, congenital muscle fiber asymmetry, distal muscular dystrophy (MD), Duchenne and Becker type MD, Emery-Dreyfus type MD, facioscapulohumeral type MD, and hyaline bodies. myopathy, limb-girdle MD, muscle sodium channel disorder, myotonic chondroplasia, myotonic dystrophy, myotubular myopathy, nemaline body disease, oculopharyngeal MD, or stress urinary incontinence;
Neuroactivation disorders include amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Guillain-Barre syndrome, Lambert-Eaton syndrome, multiple sclerosis, myasthenia gravis, nerve lesions, peripheral neuropathy, and myelopathy. muscular atrophy, delayed ulnar nerve palsy, or toxic muscle neuropathy;
Muscle fatigue disorders include chronic fatigue syndrome, diabetes (type I or type II), glycogen storage disease, fibromyalgia, Friedreich's ataxia, intermittent claudication, lipid storage myopathy, MELAS (mitochondrial encephalopathy, lactic acid encephalopathy) cis and stroke-like episodes) syndrome, mucopolysaccharidosis, Pompe disease or thyrotoxic myopathy;
The muscle mass disorder is cachexia, cartilage degeneration, cerebral palsy, compartment syndrome, severe disease myopathy, inclusion body myositis, muscular atrophy (disuse), sarcopenia, steroid myopathy, or systemic lupus erythematosus.
Mitochondrial diseases include Alpers disease, chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayla syndrome (KSS), Leber hereditary optic neuropathy (LHON), MELAS, myoclonic epilepsy and ragged red fiber disease (MERRF), neurogenic NARP, ataxia, retinitis pigmentosa, Pearson syndrome, mitochondrial dysfunction or loss of mitochondrial function,
Beta-oxidation diseases are associated with systemic carnitine transporter, carnitine palmitoyltransferase (CPT) II deficiency, very long chain acyl-CoA dehydrogenase (LCHAD or VLCAD) deficiency, trienzyme deficiency, and medium chain acyl-CoA dehydrogenase (MCAD). ) deficiency, short-chain acyl-CoA dehydrogenase (SCAD) deficiency or riboflavin-responsive disorder of β-oxidation (RR-MADD), or the metabolic disease is hyperlipidemia, dyslipidemia, hypercholesterolemia. disease, hypertriglyceridemia, HDL hypocholesterolemia, LDL hypercholesterolemia, HLD noncholesterolemia, VLDL hyperproteinemia, dyslipoproteinemia, apolipoprotein A-I hypoproteinemia, atherosclerosis sclerosis, arteriosclerotic disease, cardiovascular disease, cerebrovascular disease, peripheral circulatory system disease, metabolic syndrome, syndrome X, obesity, diabetes, type I diabetes, type II diabetes, hyperglycemia, insulin resistance, glucose tolerance dysfunction, hyperinsulinism, diabetic complications, heart failure, myocardial infarction, cardiomyopathy, hypertension, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), blood clots, Alzheimer's disease, neurodegenerative diseases in demyelinating diseases, multiple sclerosis, adrenoleukodystrophy, dermatitis, psoriasis, acne, skin aging, hirsutism, inflammation, arthritis, asthma, irritable bowel syndrome, ulcerative colitis, Crohn's disease or pancreatitis. be,
The method of embodiment 73.
75. The muscular dystrophic disease is Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, or Emery-Dreyfus muscular dystrophy. The method of embodiment 74.
76. PPAR-related disorders include abnormally low concentrations of HDL, abnormally low concentrations of apolipoprotein AI (apoA-I), abnormally high concentrations of VLDL-C, and abnormally high concentrations in the subject's plasma or serum. of low-density lipoprotein cholesterol (LDL-C), abnormally high concentrations of triglycerides, abnormally high concentrations of apolipoprotein B (apoB), abnormally high concentrations of apolipoprotein C-III (apoC-III) or lipoproteins. 56. The method of embodiment 55, wherein the ratio of hepatic lipase to protein lipase activity is abnormally low after heparin administration.
77. 56. The method of embodiment 55, wherein the PPAR-related disorder is an abnormally high concentration of HDL or an abnormally low concentration of apoA-I in the lymph or cerebrospinal fluid of the subject.
78. 56. The method of embodiment 55, wherein the obesity is abdominal obesity.
79. 56. The method of embodiment 55, wherein the cerebrovascular disease is cerebral ischemia.
80. 56. The method of embodiment 55, wherein the angiogenesis-related disorder is retinopathy or diabetes.
81. 56. The method of embodiment 55, wherein the cancer is human sarcoma or human cancer.
82. Cancers include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endosarcoma, lymphangiosarcoma, intralymphangiosarcoma, synovioma, mesothelioma, and Ewing tumor. , leiomyosarcoma, rhabdomyosarcoma, colon cancer, pancreatic cancer, bone cancer, breast cancer, ovarian cancer, prostate cancer, esophageal cancer, oral cancer, nasal cavity cancer, squamous cell carcinoma, basal cell carcinoma , adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, choriocarcinoma, seminoma, Embryonic cancer, Wilms tumor, cervical cancer, uterine cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, epithelial cancer, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependyma tumor, pinealoma, hemangioblastoma, acoustic schwannoma, oligodendroglioma, meningioma, skin cancer, melanoma, neuroblastoma, retinoblastoma, leukemia, acute B-cell lymphoblastoma leukemia, acute T-cell lymphoblastic leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia Leukemia, acute undifferentiated leukemia, chronic myeloid leukemia, hairy cell leukemia, lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, myeloid leukemia, polycythemia vera, multiple myeloma, lymphoma, Hodgkin's disease, 56. The method of embodiment 55, wherein the method is non-Hodgkin's lymphoma, Waldenström's macroglobulinemia or heavy chain disease.
83. 83. The method of embodiment 82, wherein the leukemia is acute or chronic lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, lymphocytic leukemia or myeloid leukemia.
84. 84. The method of embodiment 83, wherein the myeloid leukemia is acute and is myeloblastic leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia or erythroleukemia.
85. 84. The method of embodiment 83, wherein the lymphoma is Hodgkin's lymphoma or non-Hodgkin's lymphoma.
86. Inflammatory diseases include multiple sclerosis, chronic inflammatory disorders of the joints, arthritis, respiratory distress syndrome, inflammatory bowel disease, inflammatory lung disorders, inflammatory disorders, gingival inflammatory disorders, tuberculosis, leprosy, and kidney inflammation. 56. The method of embodiment 55, wherein the method is a sexually transmitted disease, an inflammatory disorder of the skin, an inflammatory disease of the central nervous system, systemic lupus erythematosus (SLE), or an inflammatory disease of the heart.
87. the arthritis is rheumatoid arthritis or osteoarthritis;
the inflammatory bowel disease is ileitis, ulcerative colitis or Crohn's disease;
the inflammatory lung disorder is asthma or chronic obstructive airway disease;
the inflammatory disorder of the eye is corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis or endophthalmitis;
The gingival inflammatory disorder is periodontitis or gingivitis.
The inflammatory disease of the kidney is glomerulonephritis or nephrosis,
the inflammatory disorder of the skin is acne, sclerosing dermatitis, psoriasis, eczema, photoaging or wrinkles;
The inflammatory disease of the central nervous system is AIDS-related neurodegeneration, stroke, neurotrauma, Alzheimer's disease, encephalomyelitis or viral or autoimmune encephalitis, or the inflammatory disease of the heart is cardiomyopathy.
The method of embodiment 86.
88. 56. The method of embodiment 55, wherein the neurodegenerative disease is Alzheimer's disease or Huntington's disease.
89. 56. The method of embodiment 55, wherein the autoimmune disease is immune complex vasculitis, systemic lupus or lupus erythematosus.
90. 56. The method of embodiment 55, wherein the neoplastic disease is carcinogenesis.
91. 56. The method of embodiment 55, wherein the cholestasis is an intrahepatic cholestatic disease or an extrahepatic cholestatic disease.
92. The intrahepatic cholestatic disease is primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC), or Alagille syndrome (AS). Method of Form 91.
93. 56. The method of embodiment 55, wherein the eye disease is dry eye, meibomian gland dysfunction, corneal and conjunctival epithelial disorders, corneal epithelial disorders, or corneal ulcers.
94. Lysosomal storage disorders include neuronal ceroid lipofuscinosis, Alzheimer's disease, Huntington's disease, amyotrophic spinal lateral sclerosis (ALS), Parkinson's disease, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and cerebral Corticobasal degeneration (CBD), dementia due to Lewy bodies (DLB), autophagy pathway disorders, Tea-Sachs disease, Fabry disease, Niemann-Pick disease, Gaucher disease, Hunter syndrome, alpha-mannosidosis, aspartyl 56. The method of embodiment 55, wherein the disease is glucosaminuria, cholesterol ester storage disease, chronic hexosaminidase A deficiency, cystinosis, Danon's disease, Farber's disease, fucoidosis, galactosialidosis or Batten's disease.
95. 56. The method of embodiment 55, wherein the kidney disease is renal ischemia reperfusion injury.
96. Embodiments in which the erectile dysfunction is due to damage to nerves, arteries, smooth muscle or fibrous tissue; diabetes; kidney disease; alcoholism; multiple sclerosis; atherosclerosis; vascular disease; or neurological disease. 55 methods.
97. A method for treating or preventing dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, or abnormal lipid metabolism, the method comprising administering an effective amount to a subject in need thereof. A method comprising administering a compound of any one of Forms 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
98. 98. The method of embodiment 97, wherein the hypercholesterolemia is homozygous familial hypercholesterolemia.
99. Abnormally high concentrations of high-low-density lipoprotein (LDL), apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), apolipoprotein(a), or very low-density lipoprotein (LDL) in the subject's plasma or serum. A method of treating a subject having or preventing a subject from having abnormally high levels of density lipoprotein (VLDL), comprising administering to a subject in need thereof an effective amount of embodiments 1-50. A method comprising administering any one compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
100. A method of treating a subject having, or preventing a subject from having, an abnormally low concentration of high-density lipoprotein (HDL) in the subject's plasma or serum, the method comprising: administering to a subject an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
101. A method of treating a subject having, or preventing a subject from having, an abnormally reduced or deficient lipoprotein lipase concentration or activity in the subject's plasma or serum, comprising administering to a subject in need thereof an effective amount of or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
102. 102. The method of embodiment 101, wherein the reduced or deficient lipoprotein lipase level or activity is the result of a mutation in the gene encoding lipoprotein lipase.
103. A method for treating or preventing hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial combined hyperlipidemia, the method comprising: administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound; Method.
104. Abnormally high concentrations of triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) in the subject's plasma or serum. , lipoprotein (a) (Lp(a)), apolipoprotein B, HDL/(VLDL+LDL) ratio, apolipoprotein C-II or apolipoprotein C-III, the method comprising: , an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
105. A method for improving abnormally low concentrations of high-density lipoprotein (HDL)-related protein, HDL-cholesterol, apolipoprotein AI or apolipoprotein E in the plasma or serum of a subject in need thereof. administering an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
106. The HDL-related protein is apolipoprotein AI (apoA-I), apolipoprotein A-II (apoA-II), apolipoprotein A-IV (apoA-IV), or apolipoprotein E (apoE). , the method of embodiment 105.
107. A method of promoting the clearance of triglycerides from the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable amount of said compound. A method comprising the step of administering a salt, solvate, ester, amide or prodrug.
108. A method of improving abnormally low glucose or lipid metabolism in a subject, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutically acceptable amount of the compound. A method comprising the step of administering a salt, solvate, ester, amide or prodrug.
109. 109. The method of embodiment 108, wherein the method of improving abnormally low glucose metabolism increases the subject's insulin sensitivity or oxygen consumption, or decreases blood insulin, blood sugar, or glycated hemoglobin in the subject's plasma or serum.
110. 109. The method of embodiment 108, wherein the method of improving abnormally low lipid metabolism reduces the concentration of LDL or free triglycerides or inhibits saponified or unsaponified fatty acid synthesis in the plasma or serum of the subject.
111. A method of treating or preventing symptoms of a disease selected from inflammation, systemic lupus erythematosus, lupus nephritis or arthritis, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-50; or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of said compound.
112. The method of embodiment 111, wherein the arthritis is adjuvant arthritis or type II collagen-induced arthritis.
113. The method of embodiment 111, wherein the condition is nephritis, renal failure or decreased renal function.
114. A method of reducing the fat content of meat in livestock, comprising: administering to the livestock an effective amount of a compound of any one of embodiments 1 to 50, or a pharmaceutically acceptable salt, solvate, or ester of the compound. , an amide or a prodrug.
115. A method of reducing the cholesterol content of poultry eggs, the method comprising: administering to a species of poultry an effective amount of a compound of any one of embodiments 1 to 50, or a pharmaceutically acceptable salt, solvate of said compound; A method comprising administering an ester, amide or prodrug.
116. A method of treating a subject having acute kidney injury (AKI) or at risk of AKI, the method comprising: administering to the subject an effective amount of a compound of any one of embodiments 1-50, or a pharmaceutical dosage form of the compound. A method comprising administering an acceptable salt, solvate, ester, amide or prodrug.
117. The method of embodiment 116, wherein the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, is administered intravenously, optionally for 3 days. , once daily, intravenously.
118. 117. The method of embodiment 116, wherein the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, is administered orally.
119. The method of any one of embodiments 116-118, wherein the AKI is AKI associated with sepsis.
120. The method of any one of embodiments 116-118, wherein the AKI is ischemia/reperfusion AKI.
121. The method of any one of embodiments 116-118, wherein the AKI is due to acute interstitial nephritis.
122. The method of any one of embodiments 116-118, wherein the AKI is due to a glomerular renal disease.
123. The method of any one of embodiments 116-118, wherein the AKI is due to vasculitic kidney disease.
124. The method of any one of embodiments 116-118, wherein the AKI is due to ischemia.
125. The method of any one of embodiments 116-118, wherein the AKI is due to a toxic insult.
126. The method of any one of embodiments 116-118, wherein the AKI is due to pronephric azotemia.
127. 119. The method of any one of embodiments 116-118, wherein the AKI is due to acute postrenal destructive renal injury.
128. The method of any one of embodiments 116-118, wherein the AKI is due to diabetes.
129. The method of any one of embodiments 116-118, wherein the AKI is due to underlying renal failure.
130. The method of any one of embodiments 116-118, wherein the AKI is due to a nephritic syndrome.
131. The method of any one of embodiments 116-118, wherein the AKI is due to atherosclerotic disease.
132. The method of any one of embodiments 116-118, wherein the AKI is due to hypotension.
133. The method of any one of embodiments 116-118, wherein the AKI is due to hypoxia.
134. The method of any one of embodiments 116-118, wherein the AKI is due to myoglobinuria-hematuria.
135. The method of any one of embodiments 116-118, wherein the AKI is due to liver disease.
136. The method of any one of embodiments 116-118, wherein the AKI is secondary to a viral infection, and optionally the viral infection is COVID-19.
137. 137. The method of embodiment 136, wherein the subject has a viral infection, and optionally the viral infection is COVID-19.
138. The method of 116-119, wherein the subject has sepsis.
139. 138. The method of embodiment 137, wherein the sepsis is associated with a Gram-negative bacterial infection.
140. The method of embodiment 138 or embodiment 139, wherein the subject has an intraperitoneal infection.
141. The method of embodiment 138 or embodiment 139, wherein the subject has urinary sepsis.
142. 142. The method of any one of embodiments 116-141, wherein the subject is an elderly person.
143. 143. The method of any one of embodiments 116-142, wherein the subject is a surgical patient.
144. 144. The method of embodiment 143, wherein the surgical patient undergoes cardiovascular surgery, optionally where the surgery is a coronary artery bypass graft (CABG) surgery and/or a heart valve surgery.
145. 142. The method of any one of embodiments 116-141, wherein the subject is a pregnant woman.
146. The method of any one of embodiments 116-145, wherein the subject has been exposed to a nephrotoxic agent.
147. 147. The method of embodiment 146, wherein the nephrotoxic agent comprises cisplatin, gentamicin, cephaloridine, cyclosporin, amphotericin, carbon tetrachloride, trichlorethylene, dichloroacetylene, or a combination thereof.
148. 148. The method of any one of embodiments 116-147, wherein the subject has AKI.
149. 149. The method of embodiment 148, wherein the effective amount is effective to reduce the severity of AKI.
150. 148. The method of any one of embodiments 116-147, wherein the subject is at risk of AKI.
151. 148. The method of any one of embodiments 116-147, wherein the subject is at risk for AKI after cardiovascular surgery, optionally coronary artery bypass graft (CABG) surgery and/or heart valve surgery.
152. 152. The method of embodiment 150 or embodiment 151, wherein the effective amount is effective to reduce the likelihood that the subject will develop AKI.
153. 153. The method of any one of embodiments 150-152, wherein the effective amount is effective to delay the occurrence of AKI.
154. The method of any one of embodiments 150-152, wherein the effective amount is effective to prevent AKI.
155. 153. The method of any one of embodiments 150-152, wherein if the subject develops AKI, the effective amount is effective to reduce the severity of AKI.
156. Embodiment 116, wherein the subject has a SOFA score of 1 to 4 prior to administering the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, or pharmaceutical composition. - Any one of 155 methods.
157. The method of embodiment 156, wherein the subject has a SOFA score of 2 to 4 prior to administration.
158. 157. The method of embodiment 156, wherein the subject has a SOFA score of 1 prior to administration.
159. 157. The method of embodiment 156, wherein the subject has a SOFA score of 2 prior to administration.
160. 157. The method of embodiment 156, wherein the subject has a SOFA score of 3 prior to administration.
161. 157. The method of embodiment 156, wherein the subject has a SOFA score of 4 prior to administration.
162. The method of any one of embodiments 116-161, wherein the subject has an endotoxin activity level of >0.6 prior to administration.
163. 163. The method of any one of embodiments 116-162, wherein the effective amount is effective to reduce endotoxin activity levels in the subject.

7.2. Particular Embodiments, Group 2
Various aspects of the present disclosure are described in the numbered embodiments described in the numbered paragraphs below, where references to previously numbered embodiments refer to the previous numbered embodiments in this section 7.2. refers to an embodiment in which
1. Compound of formula (C):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、フェニル、ナフチル、ピリジル、チエニル、フリル、キノリルまたはベンゾチエニルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ｒ^２は、Ｃ_２～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、またはフェニル、ナフチルもしくはピリジルにより置換されているＣ_１～６アルキルであり、これらはいずれも、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルもしくはピリジルにより置換されており、
Ａは、酸素、硫黄またはＮＲ^９であり、Ｒ^９は、水素またはＣ_１～８アルキルであり、
Ｘは、Ｃ_１～８アルキレン鎖であり、これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシもしくはヒドロキシルにより置換されており、０または１つの二重結合を有しており、
Ｙは、Ｃ（＝Ｏ）、Ｃ（＝Ｎ－ＯＲ^１０）、ＣＨ（ＯＲ^１１）、ＣＨ＝ＣＨ、Ｃ≡ＣまたはＣ（＝ＣＨ_２）であり、Ｒ^１０およびＲ^１１はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｒ^３、Ｒ^４およびＲ^５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルまたはピリジルであり、場合によりＲ^３、Ｒ^４およびＲ^５のうちの少なくとも１つは、水素ではなく、
Ｂは、ＣＨまたは窒素であり、
Ｚは、酸素または硫黄であり、
Ｒ^６およびＲ^７はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, all of which are unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy , C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
R ² is C 1 substituted by C _2-8 alkyl, C _1-8 haloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, 3-7 membered _{cycloalkyl ~8} alkyl, or C _1-6 alkyl substituted by phenyl, naphthyl or pyridyl, either unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _{1-8 alkyl 8} alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
A is oxygen, sulfur or NR ⁹ and R ⁹ is hydrogen or C _1-8 alkyl;
X is a C _1-8 alkylene chain, which is unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy or hydroxyl and has 0 or 1 double bond; and
Y is C(=O), C(=N-OR ¹⁰ ), CH(OR ¹¹ ), CH=CH, C≡C or C(=CH ₂ ), and R ¹⁰ and R ¹¹ are each hydrogen or C _1-8 alkyl,
R ³ , R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _{2 ~8} alkynyl, halogen, _C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl, optionally at least one of R ³ , R ⁴ and R ⁵ is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
２．Ｒ^１が、Ｃ_１～８アルキル、１～３個のハロゲン原子を有するＣ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲン原子を有するＣ_１～８アルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルおよびピリジルからなる群から選択される置換基を有することができるフェニルである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３．Ｒ^２が、Ｃ_２～８アルキルである、実施形態１または実施形態２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４．Ｒ^１が、第２の位置に結合しており、（ｉ）Ｒ^４が、第４位に結合しており、－－Ｘ－Ｙ－が、第５位に結合しているか、または（ｉｉ）Ｒ^４が、第５位に結合しており、－－Ｘ－－Ｙ－－が第４位に結合している、実施形態１～３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５．Ａが、酸素または硫黄である、実施形態１～４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６．Ｘが、Ｃ_１～８アルキレン鎖である、実施形態１～５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７．Ｙが、Ｃ（＝Ｏ）である、実施形態１～６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８．Ｒ^３、Ｒ^４およびＲ^５がそれぞれ、水素、Ｃ_１～８アルキルまたはハロゲンを有するＣ_１～８アルキルである、実施形態１～７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９．ＢがＣＨである、実施形態１～８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０．Ｚが、酸素である、実施形態１～９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１．Ｒ^６およびＲ^７がそれぞれ、水素またはＣ１～４アルキルである、実施形態１～１０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２．実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、フェニルまたはナフチルであり、これらはそれぞれ、Ｃ_１～８アルキル、ハロゲンを有するＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲンを有するＣ_１～８アルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルおよびピリジルからなる群から選択される１つまたは複数の置換基を有することができ、
Ｒ^２は、Ｃ_２～８アルキルであり、
Ａは、酸素または硫黄であり、
Ｘは、Ｃ_１～８アルキル置換基を有することができ、かつ二重結合を含むことができるＣ_１～８アルキレン鎖であり、
Ｙは、Ｃ（＝Ｏ）、ＣＨ＝ＣＨまたはＣ（＝ＣＨ_２）であり、
Ｒ^３、Ｒ^４およびＲ^５はそれぞれ、水素、Ｃ_１～８アルキル、ハロゲンを有するＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲンを有するＣ_１～８アルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、ハロゲン、Ｃ_２～７アシル、ベンゾイル、ヒドロキシル、ニトロ、アミノ、フェニルまたはピリジルであり、
Ｂは、ＣＨであり、
Ｚは、酸素または硫黄であり、
Ｒ^６およびＲ^７はそれぞれ、水素またはＣ_１～８アルキルである）。
１３．Ｘが、Ｃ_１～８アルキレン鎖である、実施形態１２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４．Ｒ^１が、第２の位置に結合している、実施形態１２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５．水素以外のＲ^３、Ｒ^４およびＲ^５が、Ｚに対してオルト位に位置する、実施形態１２～１４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６．Ｒ^１が、ＣＦ_３により置換されているフェニルである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７．Ｒ^２が、イソプロピルである、実施形態１もしくは実施形態１６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８．Ａが、硫黄である、実施形態１および１６～１７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９．Ｘが、ＣＨ_２ＣＨ_２である、実施形態１および１６～１８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０．Ｙが、Ｃ（＝Ｏ）である、実施形態１および１６～１９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２１．Ｙが、ＣＨ（ＯＨ）である、実施形態１および１６～１９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２２．Ｒ^３が、ＣＨ_３であり、Ｒ^４およびＲ^５がそれぞれ、水素である、実施形態１および１６～２１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２３．Ｂが、ＣＨである、実施形態１および１６～２２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２４．Ｚが、酸素である、実施形態１および１６～２３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２５．Ｒ^６およびＲ^７がそれぞれ、水素である、実施形態１および１６～２４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２６．式（Ｄ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
2. R ¹ is C _1-8 alkyl, C _1-8 alkyl having 1-3 halogen atoms, C _1-8 alkoxy, C _1-8 alkoxy having 1-3 halogen atoms, C _2-8 The compound of Embodiment 1 is phenyl which can have a substituent selected from the group consisting of alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl. , or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
3. A compound of Embodiment 1 or Embodiment 2, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ² is C _2-8 alkyl.
4. R ¹ is attached to the second position, (i) R ⁴ is attached to the fourth position, --XY- is attached to the fifth position, or (ii) ) the compound of any one of embodiments 1 to 3, wherein R ⁴ is attached to the 5-position and --X--Y-- is attached to the 4-position; Acceptable salts, solvates, esters, amides or prodrugs.
5. A compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein A is oxygen or sulfur.
6. A compound according to any one of embodiments 1-5, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is a C _1-8 alkylene chain.
7. A compound of any one of embodiments 1-6, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Y is C(=O).
8. The compound of any one of embodiments 1-7, wherein R ³ , R ⁴ and R ⁵ are each hydrogen, C _1-8 alkyl or C _1-8 alkyl with halogen, or a pharmaceutically acceptable compound thereof salts, solvates, esters, amides or prodrugs.
9. A compound of any one of embodiments 1-8, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein B is CH.
10. A compound of any one of embodiments 1-9, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Z is oxygen.
11. The compound of any one of Embodiments 1-10, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof, wherein R ⁶ and R ⁷ are each hydrogen or C1-4 alkyl. drag.
12. A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, in which
R ¹ is phenyl or naphthyl, which are respectively C _1-8 alkyl, C _1-8 alkyl with halogen, C _1-8 alkoxy, C _1-8 alkoxy with halogen, C _2-8 alkenyl, can have one or more substituents selected from the group consisting of C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl and pyridyl,
R ² is C _2-8 alkyl;
A is oxygen or sulfur;
X is a C _1-8 alkylene chain that can have a C _1-8 alkyl substituent and can contain a double bond;
Y is C(=O), CH=CH or C(=CH ₂ ),
R ³ , R ⁴ and R ⁵ each represent hydrogen, C _1-8 alkyl, C _1-8 alkyl with halogen, C _1-8 alkoxy, C _1-8 alkoxy with halogen, C _2-8 alkenyl, C _2-8 alkynyl, halogen, _C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
B is CH;
Z is oxygen or sulfur;
R ⁶ and R ⁷ are each hydrogen or C _1-8 alkyl).
13. A compound of Embodiment 12, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is a C _1-8 alkylene chain.
14. A compound of Embodiment 12, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is attached to the second position.
15. The compound of any one of embodiments 12-14, or a pharmaceutically acceptable salt, solvate thereof, wherein R ³ , R ⁴ and R ⁵ other than hydrogen are located in the ortho position to Z. , ester, amide or prodrug.
16. A compound of Embodiment 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is phenyl substituted with CF ₃ .
17. A compound of Embodiment 1 or Embodiment 16, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ² is isopropyl.
18. A compound of any one of Embodiments 1 and 16-17, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein A is sulfur.
19. A compound of any one of Embodiments 1 and 16-18, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is CH ₂ CH ₂ .
20. A compound of any one of Embodiments 1 and 16-19, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Y is C(=O).
21. A compound of any one of Embodiments 1 and 16-19, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Y is CH(OH).
22. The compound of any one of embodiments 1 and 16-21, or a pharmaceutically acceptable salt, solvate thereof, wherein R ³ is CH ₃ and R ⁴ and R ⁵ are each hydrogen. , ester, amide or prodrug.
23. A compound according to any one of Embodiments 1 and 16-22, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein B is CH.
24. A compound of any one of Embodiments 1 and 16-23, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Z is oxygen.
25. A compound of any one of Embodiments 1 and 16-24, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ⁶ and R ⁷ are each hydrogen.
26. Compound of formula (D):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１およびＲ^２は、それぞれ、独立して、水素、ハロゲン、ニトロ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、場合により置換されているＣ_６～１０アリール、Ｃ_６～１０アリール部分およびＣ_１～８アルキル部分を有するアリールアルキル基、Ｃ_１～８アルキル基を有する複素環式基または複素環式アルキル基であり、
Ｒ^３、Ｒ^４およびＲ^５は出現ごとに、独立して、水素またはＣ_１～８アルキルであり、
Ａは、酸素原子、硫黄原子またはＮＲ^３であり、
Ｘ^１、Ｘ^２およびＺはそれぞれ、独立して、Ｃ（＝Ｏ）、Ｃ（＝Ｏ）ＮＨ、Ｃ（＝Ｎ－ＯＲ^４）、ＣＨ（ＯＲ^５）、ＮＨ（Ｃ＝Ｏ）、ＮＨＳＯ_２、ＳＯ_２ＮＨ、ＣＨ＝ＣＨ、Ｃ≡Ｃまたは結合であり、
Ｙは、Ｃ_１～８アルキレンであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently hydrogen, halogen, nitro, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1-3 halogens, 1-3 halogens; C _1-8 haloalkoxy with halogen, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 alkyl substituted by 3-7 membered cycloalkyl, optionally a substituted C _6-10 aryl, an arylalkyl group having a C _6-10 aryl moiety and a C _1-8 alkyl moiety, a heterocyclic group or a heterocyclic alkyl group having a C _1-8 alkyl group;
R ³ , R ⁴ and R ⁵ at each occurrence are independently hydrogen or C _1-8 alkyl;
A is an oxygen atom, a sulfur atom or ^NR3 ,
X ¹ , X ² and Z are each independently C(=O), C(=O)NH, C(=N-OR ⁴ ), CH(OR ⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH=CH, C≡C or a bond,
Y is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
２７．Ｘ^１が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態２６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２８．Ｘ^２が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態２６もしくは実施形態２７の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２９．式（Ｅ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
27. A compound of Embodiment 26, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X ¹ is C(=O), CH(OH) or a bond.
28. A compound of embodiment 26 or embodiment 27, wherein X ² is C(=O), CH(OH) or a bond, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof; drag.
29. Compound of formula (E):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１１およびＲ^１２は、それぞれ、独立して、水素、ハロゲン、ニトロ、ヒドロキシル、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル基、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、あるいはフェニル、ナフチル、ベンジル、フェネチル、ピリジル、チエニル、フリル、キノリルまたはベンゾチエニル基（これらは、ハロゲン原子、ニトロ、ヒドロキシル、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、１～３個のハロゲンを有するＣ_１～８ハロアルコキシ、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、３～７員のシクロアルキル基、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル基、フェニルまたはピリジルである置換基を場合により有する）であり、
Ｘ^１およびＺ^１はそれぞれ、独立して、Ｃ（＝Ｏ）、Ｃ（＝Ｏ）ＮＨ、Ｃ（＝Ｎ－ＯＲ^１４）、ＣＨ（ＯＲ^１５）、ＮＨ（Ｃ＝Ｏ）、ＮＨＳＯ_２、ＳＯ_２ＮＨ、ＣＨ＝ＣＨ、Ｃ≡Ｃまたは結合であり、Ｒ^１４およびＲ^１５はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｙ^１は、Ｃ_１～８アルキレンであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹² are each independently hydrogen, halogen, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl group having 1 to 3 halogens, C _1-8 haloalkoxy group having 1 to 3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 having 3-7 membered cycloalkyl substituent ₈ alkyl, or phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl group (these are halogen atoms, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, 1- C _1-8 haloalkyl having 3 halogens, C _1-8 haloalkoxy having 1-3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl group, 3- a C _1-8 alkyl group with a 7-membered cycloalkyl substituent, optionally with a substituent that is phenyl or pyridyl);
X ¹ and Z ¹ are each independently C(=O), C(=O)NH, C(=N-OR ¹⁴ ), CH(OR ¹⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH═CH, C≡C or a bond, R ¹⁴ and R ¹⁵ are each hydrogen or C _1-8 alkyl,
Y ¹ is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
３０．Ｘ^１が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態２９の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３１．Ｚ^１が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態２９もしくは実施形態３０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３２．Ｘ^１－Ｙ^１－Ｚ^１が、フェニル環の３位または４位に結合している、実施形態２９～３１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３３．Ｘ^１が結合であり、Ｚ^１が（Ｃ＝Ｏ）である、実施形態２９～３２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３４．Ｘ^１－Ｙ^１－Ｚ^１が、５員環の４位に結合している、実施形態２９～３３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３５．Ｒ^１１が、塩素、フッ素、ヒドロキシル、１～５個の炭素原子を有するアルキル基および１～５個の炭素原子を有するアルキル基からなる群から選択される置換基を場合により有する、フェニル基またはナフチル基であり、５員環の２位に結合している、実施形態２９～３４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３６．Ｒ^１２が、３～６個の炭素原子を有するアルキル基であり、５員環の５位に結合している、実施形態２９～３５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３７．式（Ｆ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
30. A compound of Embodiment 29, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X ¹ is C(=O), CH(OH) or a bond.
31. The compound of Embodiment 29 or Embodiment 30, wherein Z ¹ is C(=O), CH(OH) or a bond, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof; drag.
32. The compound of any one of embodiments 29-31, or a pharmaceutically acceptable salt, solvate thereof, wherein X ¹ -Y ¹ -Z ¹ is attached to the 3- or 4-position of the phenyl ring. substance, ester, amide or prodrug.
33. The compound of any one of embodiments 29-32, or ^a pharmaceutically acceptable salt, solvate ^, ester, amide or prodrug.
34. the compound of any one of embodiments 29-33, or a pharmaceutically acceptable salt, solvate thereof, wherein X ¹ -Y ¹ -Z ¹ is attached to the 4-position of the 5-membered ring; Esters, amides or prodrugs.
35. R ¹¹ is a phenyl group, optionally having a substituent selected from the group consisting of chlorine, fluorine, hydroxyl, an alkyl group having 1 to 5 carbon atoms, and an alkyl group having 1 to 5 carbon atoms; The compound of any one of embodiments 29 to 34, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof, wherein the compound is a naphthyl group and is attached to the 2-position of the five-membered ring. drag.
36. The compound of any one of embodiments 29-35, or a pharmaceutically acceptable compound thereof, wherein R ¹² is an alkyl group having 3 to 6 carbon atoms and is attached to the 5-position of the 5-membered ring. salts, solvates, esters, amides or prodrugs.
37. Compound of formula (F):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ａは、Ｏ、ＳまたはＮＲ^７であり、Ｒ７は、水素またはＣ_１～８アルキルであり、
Ｂ^１は、ＣＷまたはＮであり、Ｗは、水素または結合であり、Ｂ^２は、Ｏ、ＳまたはＮＲ^８であり、Ｒ^８は、水素またはＣ_１～８アルキルであり、
Ｘ^１およびＸ^２はそれぞれ、Ｏ、Ｓ、ＮＨ、ＮＨＣ（＝Ｏ）、Ｃ（＝Ｏ）、Ｃ（＝Ｎ－ＯＲ^９）、ＣＨ（ＯＲ^１０）、Ｃ＝Ｃ、Ｃ≡Ｃまたは結合であり、Ｒ^９およびＲ^１０はそれぞれ、水素またはＣ_１～８アルキルであり、
Ｙは、Ｃ_１～８アルキレンであり、これは、無置換であるか、またはＣ_１～８アルキル、もしくは１～３個のハロゲンを有するＣ_１～８ハロアルキルにより置換されており、
Ｚは、ＮＨ、ＯまたはＳであり、
Ｒ^１は、アリール（これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、ヒドロキシル、ニトロ、アミノ、フェニル、ピリジルまたはハロゲンにより置換されている）、または１～３個のヘテロ原子を含む５～８員の環を有する複素環式基（ヘテロ原子はそれぞれ、独立して、窒素、酸素または硫黄であり、他の原子は炭素である）であり、場合により、ベンゼン環は、複素環式環と縮合しており、
Ｒ^２は、Ｃ_２～８アルキル、１～３個のハロゲンを有するＣ_１～８ハロアルキル、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、アリール（これは、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、１～３個のハロゲンを有するＣ_１～８ハロアルキル、ヒドロキシル、ニトロ、アミノ、フェニル、ピリジルもしくはハロゲンにより置換されている）により置換されているＣ_１～４アルキル、または１～３個のヘテロ原子（これらはそれぞれ、独立して、窒素、酸素または硫黄である）を有する５～８員の環を有する複素環式基により置換されているＣ_１～４アルキルであり、
Ｒ^３は、ハロゲン、トリフルオロメチル、Ｃ_１～８アルキル、Ｃ_２～８アルケニルまたはＣ_２～８アルキニルであり、
Ｒ^４およびＲ^５はそれぞれ、水素、Ｃ_１～８アルキルまたは１～３個のハロゲンを有するＣ_１～８ハロアルキルであり、
ＺおよびＲ^３はそれぞれ、ベンゼン環に結合しており、Ｘ^２は、ベンゼン環に結合しておらず、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is O, S or ^NR7 , R7 is hydrogen or _C1-8 alkyl,
B ¹ is CW or N, W is hydrogen or a bond, B ² is O, S or NR ⁸ , R ⁸ is hydrogen or C _1-8 alkyl,
X ¹ and X ² are each O, S, NH, NHC (=O), C (=O), C (=N-OR ⁹ ), CH (OR ¹⁰ ), C=C, C≡C or a bond and R ⁹ and R ¹⁰ are each hydrogen or C _1-8 alkyl,
Y is C _1-8 alkylene, which is unsubstituted or substituted with C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z is NH, O or S;
R ¹ is aryl (which is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) or a heterocyclic group having a 5- to 8-membered ring containing 1 to 3 heteroatoms, each heteroatom being independently nitrogen, oxygen, or sulfur; the other atoms are carbon), and optionally the benzene ring is fused with a heterocyclic ring;
R ² is C _2-8 alkyl, C _1-8 haloalkyl having 1-3 halogens, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, aryl (this is an unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl with 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) C _1-4 alkyl, or a heterocyclic group having a 5- to 8-membered ring having 1 to 3 heteroatoms, each of which is independently nitrogen, oxygen, or sulfur; is C _1-4 alkyl,
R ³ is halogen, trifluoromethyl, C _1-8 alkyl, C _2-8 alkenyl or C _2-8 alkynyl;
R ⁴ and R ⁵ are each hydrogen, C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z and R ³ are each bonded to a benzene ring, X ² is not bonded to a benzene ring,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
３８．Ｘ^１が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態３７の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
３９．Ｘ^２が、Ｃ（＝Ｏ）、ＣＨ（ＯＨ）または結合である、実施形態３７もしくは実施形態３８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４０．式（Ｇ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
38. A compound of Embodiment 37, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X ¹ is C(=O), CH(OH) or a bond.
39. A compound of embodiment 37 or embodiment 38, wherein X ² is C(=O), CH(OH) or a bond, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof; drag.
40. Compound of formula (G):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１およびＲ^４はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２は、水素であり、
Ｒ^３は、Ｃ_１～８アルキルであるか、またはＲ^３は、Ｒ^２と一緒になって、＝Ｏまたは＝Ｃ（Ｒ^７）（Ｒ^８）を形成し、Ｒ^７およびＲ^８はそれぞれ、同じであるか、または異なっており、水素またはＣ_１～８アルキルであり、
Ｒ^５およびＲ^６はそれぞれ、同じであるか、または異なっており、水素原子、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
ＸおよびＹは、同じであるか、または異なっており、それぞれ、ＣＨまたはＮを表し、
Ｚは、酸素または硫黄であり、
Ａは、ピラゾール、チオフェン、フランまたはピロールである５員の複素環式基であり、複素環式基は、無置換であるか、あるいはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基により置換されているＣ_１～８アルキル基、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式基である置換基を有するＣ_１～８アルキルにより置換されており、
Ｂは、Ｃ_１～８アルキレン鎖であり、これは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキルもしくはＣ_１～８ハロアルコキシにより置換されており、アルキレン基は、アルキレン基が、２～６個の炭素原子を有する場合、二重結合を場合により有しており、
ｑは、０、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ⁴ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ² is hydrogen;
R ³ is C _1-8 alkyl, or R ³ together with R ² forms =O or =C(R ⁷ )(R ⁸ ), and R ⁷ and R ⁸ are each , are the same or different and are hydrogen or C _1-8 alkyl,
R ⁵ and R ⁶ are each the same or different and are a hydrogen atom, C _1-8 alkyl, C _1-8 haloalkyl,
X and Y are the same or different and represent CH or N, respectively;
Z is oxygen or sulfur;
A is a 5-membered heterocyclic group which is pyrazole, thiophene, furan or pyrrole, and the heterocyclic group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl group substituted by a 3-7 membered cycloalkyl group, C _1-8 haloalkyl, C _1-8 haloalkoxy, A substituent that is a C _6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a 5- or 6-membered heterocyclic group substituted with C _1-8 alkyl having
B is a C _1-8 alkylene chain, which is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C Substituted by _1-8 alkoxy, halogen, C _1-8 haloalkyl or C _1-8 haloalkoxy, the alkylene group may optionally contain a double bond if the alkylene group has 2-6 carbon atoms. has,
q is 0, 1, 2, 3, 4 or 5,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
４１．Ａが、ピラゾールである、実施形態４０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４２．－（ＣＨ_２）_ｑ－が、その１位でピラゾールに結合している、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４３．－（ＣＨ_２）_ｑ－が、その３位でピラゾールに結合している、実施形態４１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４４．－Ｂ－が、その４位または５位でピラゾールに結合している、実施形態４２もしくは４３の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４５．Ａが、チオフェン、フランまたはピロールである、実施形態４０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４６．－（ＣＨ_２）_ｑ－が、その２位で５員の複素環式基に結合している、実施形態４５の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ
４７．Ａがチオフェンである、実施形態４０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４８．－（ＣＨ_２）_ｑ－が、その２位でチオフェンに結合している、実施形態４７の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
４９．ｑが０である、実施形態４０～４８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５０．ＸおよびＹがそれぞれ、ＣＨである、実施形態４０～４９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５１．Ｒ^２がＲ^３と一緒になって＝Ｏを表す、実施形態４０～５０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５２．Ｂが、１～８個の炭素原子を有するアルキル基、ならびに１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基からなる群から選択される置換基を場合により有する、２～４個の炭素原子を有するアルキレン鎖を表す、実施形態４０～５１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５３．Ｂがエチレン鎖である、実施形態４０～５２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５４．Ｒ^１およびＲ^４が、同じであるか、または異なり、それぞれが、水素原子、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、ハロゲン原子、１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルコキシ基を表す、実施形態４０～５３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５５．Ｒ^５およびＲ^６が、同じであるか、または異なり、それぞれが、水素原子または１～８個の炭素原子を有するアルキル基を表す、実施形態４０～５４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５６．Ａの場合の複素環式基に場合により結合している置換基が、１～８個の炭素原子を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基である、実施形態４０～５５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５７．式（Ｈ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
41. A compound of Embodiment 40, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein A is pyrazole.
42. A compound of Embodiment 41, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein -(CH ₂ ) _q - is attached to the pyrazole at the 1-position.
43. A compound of Embodiment 41, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein -(CH ₂ ) _q - is attached to the pyrazole at its 3-position.
44. A compound of embodiment 42 or 43, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein -B- is attached to the pyrazole at the 4- or 5-position.
45. A compound of Embodiment 40, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein A is thiophene, furan or pyrrole.
46. a compound of embodiment 45, or a pharmaceutically acceptable salt, solvate, ester thereof, wherein -(CH ₂ ) _q - is attached to a 5-membered heterocyclic group at the 2-position; Amide or prodrug 47. A compound of Embodiment 40, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein A is thiophene.
48. A compound of embodiment 47, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein -(CH ₂ ) _q - is attached to the thiophene at the 2-position.
49. A compound of any one of embodiments 40-48, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein q is 0.
50. A compound of any one of embodiments 40-49, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein X and Y are each CH.
51. A compound according to any one of embodiments 40-50, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ² together with R ³ represents =O.
52. 2 to 4 B optionally carries substituents selected from the group consisting of alkyl groups having 1 to 8 carbon atoms, and alkyl groups having 1 to 8 carbon atoms and halogen atom substituents or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of any one of embodiments 40-51, representing an alkylene chain having carbon atoms of .
53. A compound according to any one of embodiments 40-52, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein B is an ethylene chain.
54. R ¹ and R ⁴ are the same or different, and each is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a halogen atom, 1 to a compound of any one of embodiments 40 to 53, or of a compound representing an alkyl group having 8 carbon atoms and a halogen atom substituent or an alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent; Pharmaceutically acceptable salts, solvates, esters, amides or prodrugs.
55. or the compound of any one of embodiments 40 to 54, wherein R ⁵ and R ⁶ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
56. The substituent optionally attached to the heterocyclic group in A is an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent, A compound of any one of embodiments 40-55, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
57. Compound of formula (H):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１１およびＲ^１３はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^１２は、水素、Ｃ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^１４およびＲ^１５は、同じであるか、または異なっており、それぞれ、水素原子、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘ^１は、ＣＨまたはＮであり、
Ｚ^１は、酸素または硫黄であり、
Ｗ^１は、結合ａが存在する場合、酸素またはＣＨ_２であり、結合ａが存在しない場合、ＯＨであり、
ｑは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ¹² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ¹⁴ and R ¹⁵ are the same or different and each is a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ¹ is CH or N,
Z ¹ is oxygen or sulfur;
W ¹ is oxygen or CH ₂ when bond a is present, and OH when bond a is absent;
q is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
５８．Ｘ^１がＣＨである、実施形態５７の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
５９．Ｒ^１１－フェニルまたはＲ^１１－ピリジルが、１位でピラゾールに結合している、実施形態５７もしくは５８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６０．Ｒ^１１－フェニルまたはＲ^１１－ピリジルが、３位でピラゾールに結合している、実施形態５７もしくは５８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６１．－（ＣＨ_２）_ｑ－が、４位または５位でピラゾールに結合している、実施形態５７～６０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６２．Ｒ^１１およびＲ^１３が、同じであるか、または異なり、それぞれが、水素原子、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、ハロゲン原子、１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルコキシ基を表す、実施形態５７～６１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６３．Ｒ^１１およびＲ^１３が、同じであるか、または異なり、それぞれが、１～８個の炭素原子を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基を表す、実施形態５７～６１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６４．Ｒ^１４およびＲ^１５が、同じであるか、または異なり、それぞれが、水素原子または１～８個の炭素原子を有するアルキル基を表す、実施形態５７～６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６５．Ｒ^１２が、水素原子、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルコキシ基を表す、実施形態５７～６４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６６．Ｒ^１２が、１～８個の炭素原子を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基を表す、実施形態５７～６４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６７．ｑが２である、実施形態５７～６６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６８．結合ａが存在せず、Ｗ^１がＯＨである、実施形態５７～６７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
６９．結合ａが存在し、Ｗ^１が酸素である、実施形態５７～６７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７０．式（Ｊ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
58. A compound of Embodiment 57, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X ¹ is CH.
59. A compound of embodiment 57 or ^{58, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof, wherein R 11 -phenyl} or R 11 -pyridyl is attached to the pyrazole in the 1-position. drag.
60. A compound of embodiment 57 or ^{58, or a pharmaceutically acceptable salt, solvate, ester, amide or protease thereof, wherein R 11 -phenyl} or R 11 -pyridyl is attached to the pyrazole in the 3-position. drag.
61. the compound of any one of embodiments 57-60, or a pharmaceutically acceptable salt, solvate thereof, wherein -(CH ₂ ) _q - is attached to the pyrazole at the 4- or 5-position; Esters, amides or prodrugs.
62. R ¹¹ and R ¹³ are the same or different, and each is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a halogen atom, 1 to A compound of any one of embodiments 57 to 61, or a compound of any one of embodiments 57 to 61, representing an alkyl group having 8 carbon atoms and a halogen atom substituent or an alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent. Pharmaceutically acceptable salts, solvates, esters, amides or prodrugs.
63. Implementation in which R ¹¹ and R ¹³ are the same or different and each represents an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent A compound of any one of Forms 57-61, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
64. or the compound of any one of embodiments 57 to 63, wherein R ¹⁴ and R ¹⁵ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
65. R ¹² is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent, or 1 to 8 carbon atoms; A compound of any one of embodiments 57 to 64 representing an alkoxy group having 8 carbon atoms and a halogen atom substituent, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof; drag.
66. or a compound according to any one of embodiments 57 to 64, wherein R ¹² represents an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
67. A compound of any one of embodiments 57-66, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein q is 2.
68. A compound of any one of embodiments 57-67, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and W ¹ is OH.
69. A compound of any one of embodiments 57-67, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and W ¹ is oxygen.
70. Compound of formula (J):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^２１およびＲ^２３はそれぞれ、同じであるか、または異なり、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２２は、水素、Ｃ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル基置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２４およびＲ^２５は、同じであるか、または異なっており、それぞれ、水素原子、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘ^２は、ＣＨまたはＮであり、
Ｚ^２は、酸素または硫黄であり、
Ｗ^２は、結合ａが存在する場合、酸素またはＣＨ_２であり、結合ａが存在しない場合、ＯＨであり、
ｒは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ²¹ and R ²³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ²² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ²⁴ and R ²⁵ are the same or different and are each a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ² is CH or N,
Z ² is oxygen or sulfur;
^W2 is oxygen or _CH2 when bond a is present, and OH when bond a is absent;
r is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
７１．Ｘ^２がＣＨである、実施形態７０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７２．Ｒ^２１－フェニルまたはＲ^２１－ピリジルが、２位でチオフェンに結合している、実施形態７０もしくは７１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７３．Ｒ^２１およびＲ^２３が、同じであるか、または異なり、それぞれが、水素原子、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、ハロゲン原子、１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルコキシ基を表す、実施形態７０～７２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７４．Ｒ^２１およびＲ^２３が、同じであるか、または異なり、それぞれが、１～８個の炭素原子を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基を表す、実施形態７０～７２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７５．Ｒ^２４およびＲ^２５が、同じであるか、または異なり、それぞれが、水素原子または１～８個の炭素原子を有するアルキル基を表す、実施形態７０～７４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７６．Ｒ^２２が、水素原子、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルコキシ基を表す、実施形態７０～７５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７７．Ｒ^２２が、１～８個の炭素原子を有するアルキル基または１～８個の炭素原子およびハロゲン原子置換基を有するアルキル基を表す、実施形態７０～７５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７８．ｒが２である、実施形態７０～７７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
７９．結合ａが存在せず、Ｗ^２がＯＨである、実施形態７０～７８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８０．結合ａが存在し、Ｗ^２が酸素である、実施形態７０～７８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８１．式（Ｋ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
71. A compound of Embodiment 70, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X ² is CH.
72. A compound of embodiment 70 or 71, or a pharmaceutically acceptable salt, solvate, ester, amide or propane thereof, wherein R ²¹ -phenyl or R ²¹ -pyridyl is attached to the thiophene in the 2-position. drag.
73. R ²¹ and R ²³ are the same or different, and each is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a halogen atom, 1 to A compound of any one of embodiments 70 to 72, or a compound of any one of embodiments 70 to 72, representing an alkyl group having 8 carbon atoms and a halogen atom substituent or an alkoxy group having 1 to 8 carbon atoms and a halogen atom substituent. Pharmaceutically acceptable salts, solvates, esters, amides or prodrugs.
74. Implementation in which R ²¹ and R ²³ are the same or different and each represents an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent A compound of any one of Forms 70-72, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
75. or the compound of any one of embodiments 70 to 74, wherein R ²⁴ and R ²⁵ are the same or different and each represents a hydrogen atom or an alkyl group having 1 to 8 carbon atoms A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
76. R ²² is a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent, or 1 to 8 carbon atoms; A compound according to any one of embodiments 70 to 75, representing an alkoxy group having 8 carbon atoms and a halogen atom substituent, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof; drag.
77. or a compound according to any one of embodiments 70 to 75, wherein R ²² represents an alkyl group having 1 to 8 carbon atoms or an alkyl group having 1 to 8 carbon atoms and a halogen atom substituent A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
78. A compound of any one of embodiments 70-77, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein r is 2.
79. A compound of any one of embodiments 70-78, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and W ² is OH.
80. A compound of any one of embodiments 70-78, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and W ² is oxygen.
81. Compound of formula (K):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ａは、ＣＨまたは窒素であり、
Ｂは、結合ａが存在する場合、酸素またはＣ（Ｒ^８）（Ｒ^９）であり、Ｒ^８およびＲ^９はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、結合ａが存在しない場合、Ｂは、ＯＨであり、
Ｗ^１は、結合、Ｃ（＝Ｏ）または（Ｃ（Ｒ^１０）（Ｒ^１１））_ｍであり、Ｒ^１０およびＲ^１１はそれぞれ、独立して、水素またはＣ_１～８アルキル基であり、ｍは、１、２または３であり、
ＸおよびＹは、互いに異なっており、各々は、酸素原子、硫黄原子、窒素原子またはＣＲ^１２であり、Ｒ^１２は、水素またはＣ_１～８アルキルであり、
Ｚ^１は、結合、酸素、硫黄またはＣ（Ｒ^１３）（Ｒ^１４）であり、Ｒ^１３およびＲ^１４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｒ^１、Ｒ^２およびＲ^３はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^４およびＲ^５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
Ｒ^６およびＲ^７はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニルまたはＣ_１～８ハロアルキルであり、
ｒは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is CH or nitrogen,
B is oxygen or C(R ⁸ )(R ⁹ ) when bond a is present, R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and when bond a is present If not, B is OH;
W ¹ is a bond, C(=O) or (C(R ¹⁰ )(R ¹¹ )) _m , R ¹⁰ and R ¹¹ are each independently hydrogen or a C _1-8 alkyl group, m is 1, 2 or 3;
X and Y are different from each other, each is an oxygen atom, a sulfur atom, a nitrogen atom or CR ¹² , R ¹² is hydrogen or C _1-8 alkyl,
Z ¹ is a bond, oxygen, sulfur or C(R ¹³ )(R ¹⁴ ), R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
R ¹ , R ² and R ³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl or C _1-8 haloalkyl;
r is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
８２．Ａが、ＣＨ
である、実施形態８１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８３．Ｗ^１が結合である、実施形態８１もしくは８２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８４．Ｗ^１がメチレンまたはＣ（＝Ｏ）である、実施形態８１もしくは８２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８５．ＸおよびＹが、互いに異なっており、各々が、酸素原子、硫黄原子または窒素原子である、実施形態８１～８４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８６．Ｘが、硫黄原子であり、Ｙが、窒素原子である、実施形態８５の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８７．Ｚ^１が酸素原子または硫黄原子である、実施形態８１～８６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８８．Ｒ^１、Ｒ^２およびＲ^３が独立して、水素原子、１～８個の炭素原子を有するアルキル基、２～８個の炭素原子を有するアルケニル基、１～８個の炭素原子を有するアルコキシ基、ハロゲン原子、ハロゲン原子により置換されている１～８個の炭素原子を有するアルキル基またはハロゲン原子により置換されている１～８個の炭素原子を有するアルコキシ基である、実施形態８１～８７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
８９．Ｒ^４およびＲ^５がそれぞれ、独立して、水素原子またはメチルである、実施形態８１～８８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９０．Ｒ^６およびＲ^７がそれぞれ、独立して、水素原子または１～８個の炭素原子を有するアルキル基である、実施形態８１～８９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９１．ｎが２～４の整数である、実施形態８１～９０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９２．ｎが２である、実施形態９１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９３．結合ａが存在せず、ＢがＯＨである、実施形態８１～９２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９４．結合ａが存在し、Ｂが酸素である、実施形態８１～９２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９５．式（Ｌ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
82. A is CH
A compound of Embodiment 81, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
83. A compound of embodiment 81 or 82, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ¹ is a bond.
84. A compound of embodiment 81 or 82, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ¹ is methylene or C(=O).
85. The compound of any one of embodiments 81-84, or a pharmaceutically acceptable salt, solvate thereof, wherein X and Y are different from each other and each is an oxygen atom, a sulfur atom, or a nitrogen atom substance, ester, amide or prodrug.
86. A compound of Embodiment 85, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is a sulfur atom and Y is a nitrogen atom.
87. A compound of any one of embodiments 81-86, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Z ¹ is an oxygen atom or a sulfur atom.
88. R ¹ , R ² and R ³ are independently a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms; Embodiments 81 to 87, which are a group, a halogen atom, an alkyl group having 1 to 8 carbon atoms substituted by a halogen atom, or an alkoxy group having 1 to 8 carbon atoms substituted by a halogen atom or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
89. The compound of any one of embodiments 81-88, or a pharmaceutically acceptable salt, solvate, ester, amide thereof, wherein R ⁴ and R ⁵ are each independently a hydrogen atom or methyl. Or prodrugs.
90. The compound of any one of embodiments 81-89, wherein R ⁶ and R ⁷ are each independently a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, or a pharmaceutically acceptable compound of said compound. salts, solvates, esters, amides or prodrugs.
91. A compound of any one of embodiments 81-90, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein n is an integer from 2 to 4.
92. A compound of Embodiment 91, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein n is 2.
93. A compound of any one of embodiments 81-92, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and B is OH.
94. A compound according to any one of embodiments 81-92, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and B is oxygen.
95. Compound of formula (L):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｂは、結合ａが存在する場合、酸素であり、結合ａが存在しない場合、Ｂは、ＯＨであり、
Ｗ^２は、結合、Ｃ（＝Ｏ）またはＣＨ_２であり、
Ｚ^２は、酸素または硫黄であり、
Ｒ^２１、Ｒ^２２およびＲ^２３はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル；Ｃ_１～８ハロアルコキシ；ヒドロキシル、ニトロ、Ｃ_２～８アシル基、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^２４およびＲ^２５はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B is oxygen when bond a is present; B is OH when bond a is absent;
^W2 is a bond, C(=O) or _CH2 ,
Z ² is oxygen or sulfur;
R ²¹ , R ²² and R ²³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ²⁴ and R ²⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
９６．Ｗ^２が結合である、実施形態９５の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９７．Ｒ^２１、Ｒ^２２およびＲ^２３が独立して、水素原子、１～８個の炭素原子を有するアルキル基、２～８個の炭素原子を有するアルケニル基、１～８個の炭素原子を有するアルコキシ基、ハロゲン原子、ハロゲン原子により置換されている１～８個の炭素原子を有するアルキル基またはハロゲン原子により置換されている１～８個の炭素原子を有するアルコキシ基である、実施形態９５もしくは９６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９８．Ｒ^２４およびＲ^２５がそれぞれ、独立して、水素原子またはメチルである、実施形態９５～９７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
９９．結合ａが存在せず、ＢがＯＨである、実施形態９５～９８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１００．結合ａが存在し、Ｂが酸素である、実施形態９５～９８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０１．式（Ｍ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
96. A compound of Embodiment 95, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ² is a bond.
97. R ²¹ , R ²² and R ²³ are independently a hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, or an alkoxy group having 1 to 8 carbon atoms; Embodiment 95 or 96, which is a group, a halogen atom, an alkyl group having 1 to 8 carbon atoms substituted by a halogen atom, or an alkoxy group having 1 to 8 carbon atoms substituted by a halogen atom or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
98. The compound of any one of embodiments 95-97, or a pharmaceutically acceptable salt, solvate, ester, amide thereof, wherein R ²⁴ and R ²⁵ are each independently a hydrogen atom or methyl. Or prodrugs.
99. A compound of any one of embodiments 95-98, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and B is OH.
100. A compound according to any one of embodiments 95-98, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and B is oxygen.
101. Compound of formula (M):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、窒素またはＣＨであり、
Ｘは、窒素またはＣＨであり、
Ｙは、酸素または硫黄であり、
Ｚは、結合、酸素、硫黄またはＮＲ^５であり、Ｒ^５は、水素またはＣ_１～８アルキルであり、
Ｒ^１およびＲ^２はそれぞれ、独立して、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員または６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレンを有するアラルキル基または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキルであり、
Ｒ^３およびＲ^４はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ａは、ピラゾール、チオフェン、フラン、イソオキサゾール、イソチアゾールまたはピロールである５員の複素環であり、５員の複素環は、無置換であるか、あるいはハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基により置換されており、
Ｂは、結合またはＣ_１～８アルキレンであり、Ｃ_１～８アルキレンは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_１～８アルコキシもしくはハロゲン置換基により置換されており、場合により、Ｃ_１～８アルキレンは二重結合または三重結合を有しており、
ｒは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently nitrogen or CH;
X is nitrogen or CH,
Y is oxygen or sulfur;
Z is a bond, oxygen, sulfur or NR ⁵ and R ⁵ is hydrogen or C _1-8 alkyl;
R ¹ and R ² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl with 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R ³ and R ⁴ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
A is a 5-membered heterocycle that is pyrazole, thiophene, furan, isoxazole, isothiazole or pyrrole, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _{1 ~8} alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl with 3-7 membered cycloalkyl substituent, C _{1 ~8} haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a 5- or substituted with a C _1-8 alkyl group having a 6-membered heterocyclic substituent,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _1-8 alkoxy or halogen substituent optionally, the C _1-8 alkylene has a double or triple bond,
r is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１０２．Ｗ^１およびＷ^２がそれぞれ、ＣＨを表す、実施形態１０１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０３．Ｗ^１がＣＨを表し、Ｗ^２が窒素原子を表す、実施形態１０１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０４．Ｘが窒素原子を表す、実施形態１０１～１０３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０５．Ｘが窒素原子を表し、Ｙが酸素原子を表す、実施形態１０１～１０３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０６．ＸがＣＨを表し、Ｙが酸素原子を表す、実施形態１０１～１０３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０７．Ｚが酸素原子または硫黄原子を表す、実施形態１０１～１０６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０８．Ｒ^１およびＲ^２がそれぞれ、独立して、水素原子、ハロゲン原子、ヒドロキシル基、ニトロ基、アミノ基、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン置換基を有するアルキル基または１～８個の炭素原子およびハロゲン置換基を有するアルコキシ基を表す、実施形態１０１～１０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１０９．Ｒ^３およびＲ^４がそれぞれ、独立して、水素原子または１～８個の炭素原子を有するアルキル基を表す、実施形態１０１～１０８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１０．Ａが、ハロゲン原子、ヒドロキシル基、ニトロ基、アミノ基、１～８個の炭素原子を有するアルキル基、３～７員のシクロアルキル基、２～８個の炭素原子を有するアルケニル基、２～８個の炭素原子を有するアルキニル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子および３～７員のシクロアルキル置換基を有するアルキル基、１～８個の炭素原子およびハロゲン置換基を有するアルキル基、１～８個の炭素原子およびハロゲン置換基を有するアルコキシ基、６～１０個の炭素原子を有するアリール基、５員または６員の複素環式基、６～１０個の炭素原子のアリール部分および１～８個の炭素原子のアルキレン部分を有するアラルキル基、ならびに１～８個の炭素原子および５員または６員の複素環式置換基を有するアルキル基からなる群から選択される置換基を有してもよい、ピラゾール、チオフェンまたはフランを表す、実施形態１０１～１０９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１１．Ａが、ハロゲン原子、ヒドロキシル基、ニトロ基、アミノ基、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン置換基を有するアルキル基または１～８個の炭素原子およびハロゲン置換基を有するアルコキシ基からなる群から選択される置換基を有してもよい、ピラゾール、チオフェンまたはフランを表す、実施形態１０１～１０９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１２．Ａが、ハロゲン原子、ヒドロキシル基、ニトロ基、アミノ基、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン置換基を有するアルキル基、ならびに１～８個の炭素原子およびハロゲン置換基を有するアルコキシ基からなる群から選択される置換基を有してもよいピラゾールを表す、実施形態１０１～１０９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１３．Ｂが、２～４個の炭素原子を有するアルキレン鎖を表す、実施形態１０１～１１２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１４．ｎが０である、実施形態１０１～１１３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１５．式（Ｎ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
102. A compound of embodiment 101, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ¹ and W ² each represent CH.
103. A compound of embodiment 101, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ¹ represents CH and W ² represents a nitrogen atom.
104. A compound of any one of embodiments 101-103, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X represents a nitrogen atom.
105. A compound of any one of embodiments 101-103, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X represents a nitrogen atom and Y represents an oxygen atom.
106. A compound of any one of embodiments 101-103, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X represents CH and Y represents an oxygen atom.
107. A compound of any one of embodiments 101-106, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Z represents an oxygen atom or a sulfur atom.
108. R ¹ and R ² are each independently a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms; , or a compound of any one of embodiments 101 to 107, representing an alkyl group having 1 to 8 carbon atoms and a halogen substituent, or an alkoxy group having 1 to 8 carbon atoms and a halogen substituent; A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of.
109. The compound of any one of embodiments 101-108, wherein R ³ and R ⁴ each independently represent a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, or a pharmaceutically acceptable compound of said compound. salts, solvates, esters, amides or prodrugs.
110. A is a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group having 1 to 8 carbon atoms, a 3 to 7 membered cycloalkyl group, an alkenyl group having 2 to 8 carbon atoms, 2 to Alkynyl group with 8 carbon atoms, alkoxy group with 1 to 8 carbon atoms, alkyl group with 1 to 8 carbon atoms and 3 to 7 membered cycloalkyl substituent, 1 to 8 carbon atoms Alkyl groups with atoms and halogen substituents, alkoxy groups with 1 to 8 carbon atoms and halogen substituents, aryl groups with 6 to 10 carbon atoms, 5- or 6-membered heterocyclic groups, 6 From aralkyl groups having an aryl part of ~10 carbon atoms and an alkylene part of 1 to 8 carbon atoms, and alkyl groups having 1 to 8 carbon atoms and a 5- or 6-membered heterocyclic substituent. A compound of any one of embodiments 101 to 109, or a pharmaceutically acceptable salt, solvate thereof, representing pyrazole, thiophene or furan, optionally having a substituent selected from the group consisting of: , ester, amide or prodrug.
111. A is a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a halogen substituent having 1 to 8 carbon atoms; of embodiments 101 to 109 representing pyrazole, thiophene or furan, optionally having a substituent selected from the group consisting of an alkyl group having 1 to 8 carbon atoms and an alkoxy group having 1 to 8 carbon atoms and a halogen substituent. Any one compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
112. A is a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a halogen substituent having 1 to 8 carbon atoms; and a pyrazole optionally having a substituent selected from the group consisting of an alkyl group having 1 to 8 carbon atoms and a halogen substituent. A compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
113. A compound according to any one of embodiments 101 to 112, wherein B represents an alkylene chain having 2 to 4 carbon atoms, or a pharmaceutically acceptable salt, solvate, ester, amide or protein thereof. drag.
114. A compound of any one of embodiments 101-113, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein n is 0.
115. Compound of formula (N):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｗ^３は、窒素またはＣＨであり、
Ｚ^１は、酸素または硫黄であり、
Ｒ^１１およびＲ^１２はそれぞれ、独立して、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルキルまたはＣ_１～８ハロアルコキシであり、
Ｒ^１３およびＲ^１４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ａ^１は、ピラゾールまたはチオフェンである５員の複素環であり、５員の複素環は、無置換であるか、またはハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、Ｃ_１～８ハロアルキルもしくはＣ_１～８ハロアルコキシにより置換されており、
ｍは、２、３または４であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^W3 is nitrogen or CH,
Z ¹ is oxygen or sulfur;
R ¹¹ and R ¹² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl, or C _1-8 haloalkoxy;
R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
A ¹ is a 5-membered heterocycle that is pyrazole or thiophene, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 alkoxy , substituted by C _1-8 haloalkyl or C _1-8 haloalkoxy,
m is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１１６．Ｗ^３がＣＨを表す、実施形態１１５の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１７．Ａ^１が、ハロゲン原子、ヒドロキシル基、ニトロ基、アミノ基、１～８個の炭素原子を有するアルキル基、１～８個の炭素原子を有するアルコキシ基、１～８個の炭素原子およびハロゲン置換基を有するアルキル基、または１～８個の炭素原子およびハロゲン置換基を有するアルコキシ基からなる群から選択される置換基を有してもよいピラゾールを表す、実施形態１１５もしくは１１６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１８．ｍが２または３である、実施形態１１５～１１７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１１９．式（Ｏ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
116. A compound of embodiment 115, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ³ represents CH.
117. A ¹ is a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, a 1 to 8 carbon atom, and a halogen substitution A compound of embodiment 115 or 116 representing a pyrazole optionally having a substituent selected from the group consisting of an alkyl group having a group or an alkoxy group having 1 to 8 carbon atoms and a halogen substituent, or A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
118. A compound of any one of embodiments 115-117, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein m is 2 or 3.
119. Compound of formula (O):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、ＣＨまたは窒素であり、
Ｘは、ＮＲ^５またはＣＲ^６Ｒ^７であり、Ｒ^５は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシにより置換されているＣ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_３～７シクロアルキルにより置換されているＣ_１～８アルキル、フェニルにより置換されているＣ１～８アルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、Ｒ^６およびＲ^７はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｙは、（ＣＲ^８Ｒ^９）_ｒであり、Ｒ^８およびＲ^９はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、ｒは、１、２、３または４であるか、あるいは
ＸおよびＹは、一緒になって、ＣＲ^１０＝ＣＲ^１１またはエチニレンを形成し、Ｒ^１０およびＲ^１１はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｇは、結合ａが存在する場合、Ｏ、ＳまたはＣＲ^１２Ｒ^１３であり、Ｒ^１２およびＲ^１３はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、結合ａが存在しない場合、Ｇは、ＯＨであり、
Ａは、チアゾール、オキサゾール、イミダゾール、ピラゾール、チオフェン、フランまたはピロールである５員の複素環式環であり、複素環式環は、無置換であるか、あるいはＣ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基により置換されており、
Ｂは、Ｃ_１～８アルキレン鎖、Ｃ_２～８アルケニレン鎖またはＣ_２～８アルキニレン鎖であり、これらの鎖は、無置換であるか、またはＣ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_１～８アルコキシもしくはハロゲンにより置換されており、
Ｒ^１およびＲ^２はそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
Ｒ^３およびＲ^４はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
ｍは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or nitrogen;
X is NR ⁵ or CR ⁶ R ⁷ and R ⁵ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, C _{3-8 7} cycloalkyl, C _1-8 alkyl substituted by C _3-7 cycloalkyl, C 1-8 alkyl substituted by phenyl, C _2-8 acyl or C _2-8 alkenyl, R ⁶ and R each ⁷ is independently hydrogen or C _1-8 alkyl;
Y is (CR ⁸ R ⁹ ) _r , R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4, or X and Y are taken together to form CR ¹⁰ =CR ¹¹ or ethynylene, and R ¹⁰ and R ¹¹ are each independently hydrogen or C _1-8 alkyl;
G is O, S or CR ¹² R ¹³ when bond a is present, R ¹² and R ¹³ are each independently hydrogen or C _1-8 alkyl, and when bond a is absent, G is OH,
A is a 5-membered heterocyclic ring which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan or pyrrole, and the heterocyclic ring is unsubstituted or C _1-8 alkyl, C _{2-8 8} alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _{1-8 haloalkyl, C 1-8} haloalkoxy, _hydroxyl , nitro, C _2-8 acyl, C _6-10 aryl or 5-membered or 6-membered substituted with a member heterocyclic group,
B is a C _1-8 alkylene chain, a C _2-8 alkenylene chain, or a C _2-8 alkynylene chain, and these chains are unsubstituted or C _1-8 alkyl, C _3-7 cycloalkyl , substituted by C _1-8 alkoxy or halogen,
R ¹ and R ² are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
R ³ and R ⁴ are each independently hydrogen or C _1-8 alkyl;
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１２０．Ｗ^１およびＷ^２がそれぞれ、ＣＨである、実施形態１１９の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２１．Ｘが、ＣＲ^６Ｒ^７である、実施形態１１９もしくは１２０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２２．ＸがＣＨ_２である、実施形態１１９もしくは１２０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２３．ＸがＮＲ^５である、実施形態１１９もしくは１２０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２４．Ｘが、ＮＨである、実施形態１１９もしくは１２０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２５．ＸがＮＲ^３であり、Ｒ^５がＣ_１～８アルキルである、実施形態１１９もしくは１２０の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグアルキル。
１２６．ＹがＣＨ_２である、実施形態１１９～１２５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２７．Ｚがカルボキシルである、実施形態１１９～１２６のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２８．Ａが、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキル、ハロゲンにより置換されているＣ_１～８アルコキシ、ヒドロキシル、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールおよび５員または６員の複素環式基からなる群から選択される置換基により置換され得るチアゾールである、実施形態１１９～１２７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１２９．Ｂがエチレン鎖である、実施形態１１９～１２８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３０．Ｒ^１およびＲ^２がそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキルまたはハロゲンにより置換されているＣ_１～８アルコキシである、実施形態１１９～１２９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３１．Ｒ^１およびＲ^２がそれぞれ、独立して、水素、Ｃ_１～８アルキル、ハロゲン、またはハロゲンにより置換されているＣ_１～８アルキルである、実施形態１１９～１２９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３２．Ｒ^３およびＲ^４がそれぞれ、水素である、実施形態１１９～１３１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３３．ｍが０である、実施形態１１９～１３２のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３４．結合ａが存在せず、ＧがＯＨである、実施形態１１９～１３３の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３５．結合ａが存在し、Ｇが酸素である、実施形態１１９～１３３の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３６．式（Ｐ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
120. A compound of Embodiment 119, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein W ¹ and W ² are each CH.
121. A compound of embodiment 119 or 120, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is CR ⁶ R ⁷ .
122. A compound of embodiment 119 or 120, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is _CH2 .
123. A compound of embodiment 119 or 120, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is ^NR5 .
124. A compound of embodiment 119 or 120, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein X is NH.
125. A compound of embodiment 119 or 120, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug alkyl of the compound, wherein X is NR ³ and R ⁵ is C _1-8 alkyl.
126. A compound of any one of embodiments 119-125, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Y is _CH2 .
127. A compound of any one of embodiments 119-126, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Z is carboxyl.
128. A is C _1-8 alkyl, C _2-8 alkenyl, C 2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, C _1-8 alkyl substituted by _halogen; Embodiments 119-, which are thiazoles which may be substituted with substituents selected from the group consisting of ₈ alkoxy, hydroxyl, nitro, C _2-8 acyl, C _6-10 aryl and 5- or 6-membered heterocyclic groups. 127, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
129. A compound of any one of embodiments 119-128, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein B is an ethylene chain.
130. R ¹ and R ² are each independently substituted by hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, or halogen; A compound of any one of embodiments 119-129, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, which is C _1-8 alkoxy.
131. The compound of any one of embodiments 119-129, wherein R ¹ and R ² are each independently hydrogen, C _1-8 alkyl, halogen, or C _1-8 alkyl substituted with halogen, or A pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
132. A compound of any one of embodiments 119-131, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein R ³ and R ⁴ are each hydrogen.
133. A compound of any one of embodiments 119-132, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein m is 0.
134. A compound of embodiments 119-133, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and G is OH.
135. A compound of embodiments 119-133, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and G is oxygen.
136. Compound of formula (P):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｇ^ａは、結合ａが存在する場合、Ｏ、ＳまたはＣＨ_２であり、結合ａが存在しない場合、Ｇ^ａは、ＯＨであり、
Ａ^ａは、チアゾール、オキサゾールまたはチオフェンである５員の複素環式環であり、５員の複素環式環は、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロもしくはＣ_２～８アシルにより置換されており、
Ｂ^ａは、Ｃ_１～８アルキレン鎖またはＣ_２～８アルケニレン鎖であり、
Ｒ^１ａおよびＲ^２ａはそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロまたはＣ_２～８アシルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^a is O, S or CH ₂ when bond a is present; when bond a is absent, G ^a is OH;
A ^a is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, halogen , C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^a is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1a and R ^2a are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１３７．Ａ^ａが、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキル、ハロゲンにより置換されているＣ_１～８アルコキシ、ヒドロキシル、ニトロおよびＣ_２～８アシルからなる群から選択される置換基により置換され得るチアゾールである、実施形態１３６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３８．Ｂ^ａが、エチレン鎖である、実施形態１３６もしくは１３７の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１３９．Ｒ^１ａおよびＲ^２ａがそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキルまたはハロゲンにより置換されているＣ_１～８アルコキシである、実施形態１３６～１３８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４０．結合ａが存在せず、Ｇ^ａがＯＨである、実施形態１３６～１３９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４１．結合ａが存在し、Ｇ^ａが酸素である、実施形態１３６～１３９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４２．式（Ｑ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
137. A ^a is C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, C _1-8 alkoxy substituted by halogen, hydroxyl, nitro and C _2-8 A compound of embodiment 136, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, which is a thiazole which may be substituted with a substituent selected from the group consisting of acyl.
138. A compound of embodiment 136 or 137, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein B ^a is an ethylene chain.
139. R ^1a and R ^2a are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, or C _1-8 substituted by halogen; A compound of any one of embodiments 136-138 that is alkoxy, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
140. A compound of any one of embodiments 136-139, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and G ^a is OH.
141. A compound according to any one of embodiments 136-139, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and G ^a is oxygen.
142. Compound of formula (Q):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｇ^ｂは、結合ａが存在する場合、Ｏ、ＳまたはＣＨ_２であり、結合ａが存在しない場合、Ｇ^ｂは、ＯＨであり、
Ａ^ｂは、チアゾール、オキサゾールまたはチオフェンである５員の複素環式環であり、５員の複素環式環は、無置換であるか、またはＣ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロもしくはＣ_２～８アシルにより置換されており、
Ｂ^ｂは、Ｃ_１～８アルキレン鎖またはＣ_２～８アルケニレン鎖であり、
Ｒ^１ｂおよびＲ^２ｂはそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ヒドロキシル、ニトロまたはＣ_２～８アシルであり、
Ｒ^３ｂは、水素またはＣ_１～８アルキルであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^b is O, S or CH ₂ when bond a is present, and G ^b is OH when bond a is absent;
A ^b is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, halogen , C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^b is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1b and R ^2b are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^3b is hydrogen or C _1-8 alkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１４３．Ａ^ｂが、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキル、ハロゲンにより置換されているＣ_１～８アルコキシ、ヒドロキシル、ニトロおよびＣ_２～８アシルからなる群から選択される置換基により置換されているチアゾールである、実施形態１４２の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４４．Ｂ^ｂが、エチレン鎖である、実施形態１４２もしくは１４３の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４５．Ｒ^１ｂおよびＲ^２ｂがそれぞれ、独立して、水素、Ｃ_１～８アルキル、Ｃ_１～８アルコキシ、ハロゲン、ハロゲンにより置換されているＣ_１～８アルキルまたはハロゲンにより置換されているＣ_１～８アルコキシである、実施形態１４２～１４４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４６．結合ａが存在せず、Ｇ^ｂがＯＨである、実施形態１４２～１４５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４７．結合ａが存在し、Ｇ^ｂが酸素である、実施形態１４２～１４５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１４８．式（Ｒ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
143. A ^b is C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, C _1-8 alkoxy substituted by halogen, hydroxyl, nitro and C _2-8 A compound of embodiment 142, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, is a thiazole substituted with a substituent selected from the group consisting of acyl.
144. A compound of embodiment 142 or 143, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein B ^b is an ethylene chain.
145. R ^1b and R ^2b are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 alkyl substituted by halogen, or C _1-8 substituted by halogen; A compound of any one of embodiments 142-144 that is alkoxy, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
146. A compound of any one of embodiments 142-145, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and G ^b is OH.
147. A compound of any one of embodiments 142-145, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, wherein bond a is present and G ^b is oxygen.
148. Compound of formula (R):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｗ^１およびＷ^２はそれぞれ、独立して、ＣＨまたはＮであり、
Ｘは、ＮＲ^３またはＣＲ^４Ｒ^５であり、Ｒ^３は、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシにより置換されているＣ_１～８アルキル、３～７員のシクロアルキルにより置換されているＣ_１～８アルキル、フェニル基により置換されているＣ_１～８アルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｒ^４およびＲ^５はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、
Ｙは、（ＣＲ^６Ｒ^７）_ｒであり、Ｒ^６およびＲ^７はそれぞれ、独立して、水素またはＣ_１～８アルキルであり、ｒは、１、２、３または４であり、
Ａは、チアゾール、オキサゾール、イミダゾール、ピラゾール、チオフェン、フラン、ピロール、ピリジンまたはピリミジンである５員もしくは６員の複素環式基あるいはフェニル基であり、５員もしくは６員の複素環式基またはフェニル基は、無置換であるか、あるいはＣ_１～８アルキル、３～７員のシクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシル、３～７員のシクロアルキル基により置換されているＣ_１～８アルキル基、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、Ｃ_６～１０アリール、５もしくは６員の複素環式基、Ｃ_６～１０アリール基およびＣ_１～８アルキル基を含むアラルキル基、または５員もしくは６員の複素環式基により置換されているＣ_１～８アルキル基により置換されており、
Ｂは、結合またはＣ_１～８アルキレンであり、Ｃ_１～８アルキレンは、無置換であるか、またはＣ_１～８アルキル、３～７員のシクロアルキル基、Ｃ_１～８アルコキシもしくはハロゲンにより置換されており、かつアルキレン鎖の炭素数が２個以上である場合、二重結合または三重結合を有してもよく、
Ｄは、ＮまたはＣＨであり、
Ｅは、ＯまたはＳであり、
Ｒ^１およびＲ^２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、ハロゲン、Ｃ_１～８ハロアルキル、Ｃ_１～８ハロアルコキシ、ニトロ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたは５員もしくは６員の複素環式基であり、
ｍは、０、１、２または３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or N,
X is NR ³ or CR ⁴ R ⁵ and R ³ is C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, 3-7 membered C _1-8 alkyl substituted by cycloalkyl, C _1-8 alkyl substituted by phenyl group, C _2-8 acyl or C _2-8 alkenyl,
R ⁴ and R ⁵ are each independently hydrogen or C _1-8 alkyl;
Y is (CR ⁶ R ⁷ ) _r , R ⁶ and R ⁷ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4;
A is a 5- or 6-membered heterocyclic group that is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, pyrrole, pyridine or pyrimidine, or a phenyl group; A is a 5- or 6-membered heterocyclic group or phenyl; The group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxyl, 3-7 membered cycloalkyl group. C _{1-8 alkyl group, C 1-8 haloalkyl} , C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _{6-10 aryl group and C 1-8 aryl} group substituted with substituted by an aralkyl group containing _~8 alkyl group, or a C _1-8 alkyl group substituted by a 5- or 6-membered heterocyclic group,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or substituted by C _1-8 alkyl, 3-7 membered cycloalkyl group, C _1-8 alkoxy or halogen. If it is substituted and the number of carbon atoms in the alkylene chain is 2 or more, it may have a double bond or triple bond,
D is N or CH;
E is O or S;
R ¹ and R ² are each independently H, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１４９．式（Ｓ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
149. Compound of formula (S):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ａ^１は、チアゾール、オキサゾール、ピリジンもしくはピリミジンである５員または６員の複素環式基、あるいはフェニル基であり、５もしくは６員の複素環式基またはフェニル基は、無置換であるか、またはＣ_１～８アルキルまたはＣ_１～８ハロアルキルにより置換されており、
Ｂ^１は、Ｃ_２～４アルキレンであり、
Ｒ^１１およびＲ^１２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、ハロゲンまたはＣ_１～８ハロアルキルであり、
Ｒ^１３は、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、場合によりＲ^１３が結合しているＮは、ベンゾイソオキサゾールの第６位に結合しており、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A ¹ is a 5- or 6-membered heterocyclic group such as thiazole, oxazole, pyridine or pyrimidine, or a phenyl group, and the 5- or 6-membered heterocyclic group or phenyl group is unsubstituted or or substituted with C _1-8 alkyl or C _1-8 haloalkyl,
B ¹ is C _2-4 alkylene;
R ¹¹ and R ¹² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ¹³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ¹³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１５０．式（Ｔ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
150. Compound of formula (T):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｂ^２は、Ｃ_２～４アルキレンであり、
Ｒ^２０は、Ｃ_１～８アルキルであり、
Ｒ^２１およびＲ^２２はそれぞれ、独立して、Ｈ、Ｃ_１～８アルキル、ハロゲンまたはＣ_１～８ハロアルキルであり、
Ｒ^２３は、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、場合によりＲ^２３が結合しているＮは、ベンゾイソオキサゾールの第６位に結合しており、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B ² is C _2-4 alkylene;
R ²⁰ is C _1-8 alkyl;
R ²¹ and R ²² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ²³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ²³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルであり、
ｎは、０、１、２、３または４である）。
１５１．式（Ｕ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4).
151. Compound of formula (U):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^３、Ｒ^４、Ｒ^５およびＲ^６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｘは、酸素、硫黄またはＮＲ^７であり、Ｒ^７は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｙは、酸素、硫黄、ＮＲ^８または結合であり、Ｒ^８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
ｐは、０または１であり、
Ａは、結合ａが存在する場合、酸素 ＣＨ_２、Ｎ－ＮＨ_２またはＮ－ＯＲ^９であり、Ｒ^９は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシル、Ｃ_２～８アルケニルまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、結合ａが存在しない場合、Ａは、ＯＨであり、
Ｂは、ｐ＝１である場合、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、もしくはＣ_６～１０アリール部分および１～８個の炭素原子のＣ１－Ｃ８のアルキレン部分を有するアラルキル基である置換基を有するまたは有さないベンゼン環であり、ｐ＝０の場合、インドール、ベンゾフラン、ベンゾイソオキサゾールまたは１，２－ベンゾイソチアゾールである縮合環であり、前記縮合環は、置換基を有するか、または有しておらず、この置換基は、
ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ１－Ｃ８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ基、Ｃ_２～８アシル、Ｃ_６～１０アリール、またはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｙは、Ｂのベンゼン環に結合しており、
（Ｃ（Ｒ^３）（Ｒ^４））_ｍは、その３位においてＢの縮合環に結合しており、
ｍは、１～４の整数であり、
ｎは、０、１、２、３、４または５であり、
Ｙは、ｎ＝０の場合、結合であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C _1-8 alkyl, C _3-7 cycloalkyl, C2-C8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3- C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ² has hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _1-8 alkyl with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
X is oxygen, sulfur or NR ⁷ and R ⁷ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, C _{2 ~8} acyl or C _2-8 alkenyl,
Y is oxygen, sulfur, NR ⁸ or a bond, R ⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
p is 0 or 1,
A is oxygen CH ₂ , N-NH ₂ or N-OR ⁹ when bond a is present, R ⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl, an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A is OH;
When p=1, B is halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3 C 1-8 alkyl having ~7-membered cycloalkyl substituent, C _1-8 haloalkyl _{, C 1-8 alkyl} having C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, a benzene ring with or without substituents that is a C _6-10 aryl group or an aralkyl group having a C _6-10 aryl moiety and a C1-C8 alkylene moiety of 1 to 8 carbon atoms; p= If 0, it is a fused ring which is indole, benzofuran, benzisoxazole or 1,2-benziisothiazole, said fused ring has or does not have a substituent, and this substituent is
Halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl with C1-C8 alkoxy substituent, C _1-8 haloalkoxy group, C _2-8 acyl, C _6-10 aryl, or C ₆ an aralkyl group having _~10 aryl moieties and a C _1-8 alkylene moiety;
Y is bonded to the benzene ring of B,
(C(R ³ )(R ⁴ )) _m is bonded to the fused ring of B at its 3-position,
m is an integer from 1 to 4,
n is 0, 1, 2, 3, 4 or 5;
Y is a bond when n=0,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１５２．結合ａが存在せず、ＡがＯＨである、実施形態１５１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５３．結合ａが存在し、Ａが酸素である、実施形態１５１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５４．式（Ｖ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
152. A compound of embodiment 151, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and A is OH.
153. A compound of Embodiment 151, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and A is oxygen.
154. Compound of formula (V):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^１２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^１３、Ｒ^１４、Ｒ^１５およびＲ^１６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｙ^１は、酸素、硫黄、ＮＲ^１８または結合であり、Ｒ^１８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ａ^１は、結合ａが存在する場合、酸素 ＣＨ_２、Ｎ－ＮＨ_２またはＮ－ＯＲ^１９であり、Ｒ^１９は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシル、Ｃ_２～８アルケニルまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、結合ａが存在しない場合、Ａ^１は、ＯＨであり、
Ｑ^１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
ｒは、１、２、３または４であり、
ｓは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R11 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ¹² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ¹ is oxygen, sulfur, NR ¹⁸ or a bond, R ¹⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl,
A ¹ is oxygen CH ₂ , N-NH ₂ or N-OR ¹⁹ when bond a is present, R ¹⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl , an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A ¹ is OH;
Q ¹ is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
r is 1, 2, 3 or 4;
s is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１５５．結合ａが存在せず、Ａ^１がＯＨである、実施形態１５４の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５６．結合ａが存在し、Ａ^１が酸素である、実施形態１５４の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１５７．式（Ｗ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
155. A compound of embodiment 154, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is absent and A ¹ is OH.
156. A compound of embodiment 154, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein bond a is present and A ¹ is oxygen.
157. Compound of formula (W):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^２１は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、シアノ、カルボキシル、Ｃ_１～８アルキル、Ｃ_３～７シクロアルキル、Ｃ２～Ｃ８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリール基、５員もしくは６員の複素環式基、Ｃ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基、または５員もしくは６員の複素環式置換基を有するＣ_１～８アルキル基であり、
Ｒ^２２は、水素、Ｃ_１～８アルキル、Ｃ_２～８アルケニル、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル基、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
Ｒ^２３、Ｒ^２４、Ｒ^２５およびＲ^２６はそれぞれ、独立して、水素、Ｃ_１～８アルキルまたはＣ_１～８ハロアルキルであり、
Ｙ^２は、酸素、硫黄、ＮＲ^２８または結合であり、Ｒ^２８は、水素、Ｃ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_２～８アシルまたはＣ_２～８アルケニルであり、
Ｑ^２は、水素、ハロゲン、ヒドロキシル、ニトロ、アミノ、Ｃ_１～８アルキル基、Ｃ_３～７シクロアルキル、Ｃ_２～８アルケニル、Ｃ_２～８アルキニル、Ｃ_１～８アルコキシ、３～７員のシクロアルキル置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルキル、Ｃ_１～８アルコキシ置換基を有するＣ_１～８アルキル、Ｃ_１～８ハロアルコキシ、Ｃ_２～８アシル、Ｃ_６～１０アリールまたはＣ_６～１０アリール部分およびＣ_１～８アルキレン部分を有するアラルキル基であり、
ｔは、１、２、３または４であり、
ｕは、１、２、３、４または５であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R21 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ²² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ² is oxygen, sulfur, NR ²⁸ or a bond, R ²⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
Q ² is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
t is 1, 2, 3 or 4,
u is 1, 2, 3, 4 or 5,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１５８．式（Ｘ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
158. Compound of formula (X):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１５９．式（Ｙ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
159. Compound of formula (Y):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted with alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１６０．式（Ｚ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
160. Compound of formula (Z):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｑ^１は、ＣＨまたはＮであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、１または２であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^２０はそれぞれ、独立して、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^３は、ＣＨ_３またはＣＤ_３であり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted with alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１６１．Ｒ^３がＣＨ_３である、実施形態１５８～１６０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６２．Ｑ^１がＣＨである、実施形態１５８～１６１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６３．Ｑ^１がＮである、実施形態１５８～１６１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６４．Ｒ^２が、ハロゲン、－С_１～С_４－アルキル、－С_１～С_４－ハロアルキル、－С_１～С_４－ハロアルコキシ、－Ｓ（С_１～С_４－アルキル）またはフラニルであり、フラニルが、－С_１～С_４－アルキルにより場合により置換され得る、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６５．Ｒ^２が、ハロゲン、－ＣＨ_３、－Ｃ_１－ハロアルキル、－Ｃ_１－ハロアルコキシ、－ＳＣＨ_３またはフラニルであり、フラニルが、－ＣＨ_３により場合により置換され得る、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６６．Ｒ^２が、ハロゲン、－ＣＨ_３、－Ｃ_１－ハロアルキル、－Ｃ_１－ハロアルコキシまたは－ＳＣＨ_３である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６７．Ｒ^２が、クロロ、無置換フラニル、－ＣＨ_３、－ＣＦ_３、－ＯＣＦ_３、－ＯＣＨＦ_２または－ＳＣＨ_３である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６８．Ｒ^２が、－ＣＦ_３または－ＯＣＦ_３である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１６９．Ｒ^２が－ＣＦ^３である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７０．Ｒ^１が、水素またはハロゲンである、実施形態１５８～１６９のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７１．Ｒ^１が、水素またはフルオロである、実施形態１５８～１７０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７２．Ｒ^２０はそれぞれ、独立して、水素またはハロゲンである、実施形態１５８～１７１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７３．Ｒ^２０が、水素またはフルオロである、実施形態１５８～１７１のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７４．Ｒ^１が、水素またはフルオロであり、Ｒ^２が、С_１～С_４－ハロアルキルまたはС_１～С_４－ハロアルコキシであり、Ｒ^２０が、水素であり、ｘが、１の値を有する整数である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７５．Ｒ^１が、水素であり、Ｒ^２が、トリフルオロメチルまたはトリフルオロメトキシであり、Ｒ^２０が、水素であり、ｘが、１の値を有する整数である、実施形態１５８～１６３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７６．式（ＡＡ）の化合物：

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
161. A compound of any one of embodiments 158-160, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ³ is CH ₃ .
162. A compound of any one of embodiments 158-161, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein Q ¹ is CH.
163. A compound of any one of embodiments 158-161, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein Q ¹ is N.
164. R ² is halogen, -С ₁ -С ₄ -alkyl, -С ₁ -С ₄ -haloalkyl, -С ₁ -С ₄ -haloalkoxy, -S (С ₁ -С ₄ -alkyl) or furanyl, A compound of any one of embodiments _158-163 , or a pharmaceutically acceptable salt, solvate _, ester, amide or prodrug.
165. of embodiments 158-163, wherein R ² is halogen, -CH ₃ , -C ₁ -haloalkyl, -C ₁ -haloalkoxy, -SCH ₃ or furanyl, and furanyl may be optionally substituted by -CH ₃ Any one compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
166. The compound of any one of embodiments 158-163, wherein R ² is halogen, -CH ₃ , -C ₁ -haloalkyl, -C ₁ -haloalkoxy or -SCH ₃ , or a pharmaceutically acceptable compound thereof salts, solvates, esters, amides or prodrugs.
167. The compound of any one of embodiments 158-163, wherein R ² is chloro, unsubstituted furanyl, -CH ₃ , -CF ₃ , -OCF ₃ , -OCHF ₂ or -SCH ₃ , or the pharmaceutical composition of the compound Acceptable salts, solvates, esters, amides or prodrugs.
168. A compound of any one of embodiments 158-163, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ² is -CF ₃ or -OCF ₃ .
169. A compound of any one of embodiments 158-163, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ² is -CF ³ .
170. A compound of any one of embodiments 158-169, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is hydrogen or halogen.
171. A compound of any one of embodiments 158-170, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is hydrogen or fluoro.
172. A compound of any one of embodiments 158-171, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein each R ²⁰ is independently hydrogen or halogen.
173. A compound of any one of embodiments 158-171, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ²⁰ is hydrogen or fluoro.
174. R ¹ is hydrogen or fluoro, R ² is С ₁ -С ₄ -haloalkyl or С ₁ -С ₄ -haloalkoxy, R ²⁰ is hydrogen, and x is an integer having a value of 1 A compound of any one of embodiments 158-163, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.
175. Any of embodiments 158-163, wherein R ¹ is hydrogen, R ² is trifluoromethyl or trifluoromethoxy, R ²⁰ is hydrogen, and x is an integer having a value of 1. A compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
176. Compound of formula (AA):

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ
（式中、
Ｌは、（ＣＨ_２）_５であり、これは、無置換であるか、または１つのメチル基によって置換されており、
Ｒ^１は、水素、ハロゲン、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、ＣＮ、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシまたはＣ_３～６シクロアルキルであり、
Ｒ^２は、水素、ハロゲン、ＣＮ、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキル、Ｃ_３～６シクロアルキル、Ｃ_１～４アルコキシ、Ｃ_１～４ハロアルコキシ、Ｓ（Ｃ_１～４アルキル）、ＳＯ_２（Ｃ_１～４－アルキル）、５員もしくは６員の複素環、アリール、５員のヘテロアリール、Ｃ≡Ｃ－Ｒ^２Ａ、Ｏ（ＣＨ_２）_ｍＲ^２Ｂ、ＮＨ（Ｃ_１～４アルキル）、Ｎ（Ｃ_１～４アルキル）_２またはＣ（Ｏ）（Ｃ_１～４アルキル）であり、アリールおよびヘテロアリールは、無置換であるか、またはハロゲン、ＯＨ、ＣＮ、Ｃ_１～４アルキル、ホルミル、アセチル、アセトキシもしくはカルボキシにより置換されており、ｍは、１、２または３であり、
ｘは、０または１であり、
Ｒ^２ＡおよびＲ^２Ｂは、それぞれ独立して、Ｃ_１～４アルキル、Ｃ_１～４ハロアルキルまたはＣ_３～６シクロアルキルであり、
Ｒ^３は、Ｃ_１～４ハロアルキル、ＮＯ_２、ＣＮ、ハロゲンまたはＣ（Ｏ）Ｏ（Ｃ_１～４アルキル）であり、
Ｒ^２０は、水素、ハロゲン、Ｃ_１～４アルキル、ＣＮまたはＣ_１～４アルコキシであり、
Ｒ^Ｘは、ＣＨ_２ＯＨ、ＣＯＨ、ＣＯＯＣＨ_２ＣＯＮＲ^Ｘ４Ｒ^Ｘ５、ＳＯ_３Ｈ

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
L is (CH ₂ ) ₅ , which is unsubstituted or substituted with one methyl group,
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted with alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 0 or 1,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
R ³ is C _1-4 haloalkyl, NO ₂ , CN, halogen or C(O)O (C _1-4 alkyl),
R ²⁰ is hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

であり、
Ｒ^Ｘ４およびＲ^Ｘ５はそれぞれ、独立して、アルキル、アリールもしくはヘテロアリールであるか、または代替的に、Ｒ^Ｘ４およびＲ^Ｘ５は、Ｒ^Ｘ４およびＲ^Ｘ５が結合している炭素原子と一緒になって、複素環を形成し、
Ｒ^Ｘ６およびＲ^Ｘ７はそれぞれ、独立して、Ｈ、Ｃ_１～６アルキル、Ｃ_２～６アルケニルまたはＣ_２～６アルキニルである）。
１７７．式

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl).
177. formula

を有する、実施形態１７６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７８．式

176, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.
178. formula

を有する、実施形態１７６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１７９．Ｒ^３が、ハロメチル、ＣＮまたはハロゲンである、実施形態１７６～１７８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８０．Ｒ^３が、ＣＦ_３、ＣｌまたはＣＮである、実施形態１７６～１７８のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８１．Ｒ^２が、水素、ハロゲン、ＣＮ、Ｃ_１～Ｃ_４－アルキル、Ｃ_１～Ｃ_４アルコキシ、Ｃ_１～Ｃ_４－ハロアルキル、Ｃ_１～Ｃ_４－ハロアルキル、Ｓ（Ｃ_１～Ｃ_４－アルキル）またはフラニルであり、フラニルが、Ｃ_１～Ｃ_４－アルキルにより場合により置換され得、ｘが０または１である、実施形態１７６～１８０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８２．Ｒ^２が、Ｈ、ハロゲン、ＣＮ、ＣＨ_３、ハロメチル、ハロメトキシ、メトキシまたはフラニルであり、フラニルが、ＣＨ_３により場合により置換され得、Ｒ^２０が、メチルまたはハロゲンである、実施形態１７６～１８０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８３．Ｒ^２が、Ｈ、Ｆ、Ｃｌ、ＣＮ、ＣＦ_３、ＯＣＦ_３またはフラニルであり、ｘが０である、実施形態１７６～１８０のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８４．Ｒ^１が水素である、実施形態１７６～１８３のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８５．Ｒ^１が、水素またはフルオロである、実施形態１７６～１８４のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８６．Ｒ^Ｘが、ＣＨ_２ＯＨ、ＣＯＨまたはＣＯＯＣＨ_２ＣＯＮＲ^４Ｒ^５である、実施形態１～１８５のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８７．Ｒ^ＸがＣＨ_２ＯＨである、実施形態１８６の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８８．実施形態１～１５１のいずれか１つに従属する場合、ｎが０である、実施形態１～１８７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１８９．実施形態１～１５１のいずれか１つに従属する場合、ｎが１である、実施形態１～１８７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９０．

176, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.
179. A compound of any one of embodiments 176-178, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ³ is halomethyl, CN or halogen.
180. A compound of any one of embodiments 176-178, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ³ is CF ₃ , Cl or CN.
181. R ² is hydrogen, halogen, CN, C ₁ -C ₄ -alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -haloalkyl, S(C ₁ -C ₄ -alkyl) ) or furanyl, and the furanyl may be optionally substituted by C ₁ -C ₄ -alkyl, and x is 0 or 1; Acceptable salts, solvates, esters, amides or prodrugs.
182. Embodiments 176-180, wherein R ² is H, halogen, CN, CH ₃ , halomethyl, halomethoxy, methoxy or furanyl, furanyl may be optionally substituted with CH ₃ and R ²⁰ is methyl or halogen. or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
183. The compound of any one of embodiments 176-180, or a pharmaceutically acceptable compound thereof, wherein R ² is H, F, Cl, CN, CF ₃ , OCF ₃ or furanyl, and x is 0 salts, solvates, esters, amides or prodrugs.
184. A compound of any one of embodiments 176-183, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is hydrogen.
185. A compound of any one of embodiments 176-184, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ¹ is hydrogen or fluoro.
186. The compound of any one of embodiments 1-185, or a pharmaceutically acceptable salt, solvate, ester, amide thereof, wherein R ^X is CH ₂ OH, COH or COOCH ₂ CONR ⁴ R ⁵ Or prodrugs.
187. A compound of embodiment 186, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, wherein R ^X is CH ₂ OH.
188. When dependent on any one of embodiments 1-151, the compound of any one of embodiments 1-187, or a pharmaceutically acceptable salt, solvate, ester of said compound, where n is 0 , amide or prodrug.
189. A compound of any one of Embodiments 1-187, or a pharmaceutically acceptable salt, solvate, ester of said compound, when dependent on any one of Embodiments 1-151, where n is 1 , amide or prodrug.
190.

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９１．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. drag.
191.

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９２．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. drag.
192.

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９３．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. drag.
193.

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである、実施形態１の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９４．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. drag.
194.

または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグである、実施形態１５８の化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９５．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. drag.
195.

である化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９６．

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
196.

である化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９７．表１に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９８．表２に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
１９９．表３に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２００．表４に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０１．表５に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０２．表６に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０３．表７に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０４．表８に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０５．表９に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０６．表１０に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０７．表１１に示されている化合物から選択される化合物、または薬学的に許容されるその塩、溶媒和物、エステル、アミドもしくはプロドラッグ。
２０８．実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩。
２０９．アルカリ金属塩であり、場合によりナトリウム塩またはカリウム塩である、実施形態１～２０７のいずれか１つの化合物の薬学的に許容される塩。
２１０．実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、および薬学的に許容される担体またはビヒクルを含む、医薬組成物。
２１１．第２の治療活性剤をさらに含む、実施形態２１０の医薬組成物。
２１２．第２の治療活性剤が、脂質低下薬、スタチン、コレステロール吸収阻害剤、ＰＣＳＫ９に対する抗体、ｓｉＲＮＡ ＰＣＳＫ９、抗線維化剤、甲状腺ホルモン、選択的甲状腺受容体－βアゴニスト、アポトーシスシグナル調節性キナーゼ１（ＡＳＫ１）阻害剤、アセチル－ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害剤、インテグリンアンタゴニストまたは非ステロイド系ファルネソイドＸ受容体（ＦＸＲ）アゴニストである、実施形態２１１の医薬組成物。
２１３．脂質低下薬が、ゲムフィブロジル、フェノフィブレート、ベザフィブレート、クロフィブレート、シプロフィブレート、クリノフィブラート、エトフィリン、ピリフィブラート、シムフィブラート、トコフィブラートまたはペマフィブラートである、スタチンが、アトルバスタチン、シンバスタチン、プラバスタチン、ロスバスタチン、フルバスタチン、ロバスタチン、ピタバスタチン、メバスタチン、ダルバスタチン、ジヒドロコンパクチンもしくはセリバスタチンである、または薬学的に許容されるそれらの塩、溶媒和物、エステル、アミドもしくはプロドラッグである、コレステロール吸収阻害剤が、エゼチミブであり、ＰＣＳＫ９に対する抗体が、エボロクマブ アルイロクマブ、ボコシズマブ、１Ｄ０５－ＩｇＧ２、ＲＧ７６５２、ＬＹ３０１５０１４またはＬＧＴ－２０９である、ｓｉＲＮＡ ＰＣＳＫ９が、インクリシランであり、抗線維化剤が、ニタゾキサミド、チゾキサニドもしくはチゾキサニドグルクロニド、または薬学的に許容されるそれらの塩、溶媒和物、エステル、アミドもしくはプロドラッグである、選択的甲状腺受容体－βアゴニストが、ＶＫ２８０９、ＭＧＬ－３１９６、ＭＧＬ－３７４５、ＳＫＬ－１４７６３、ソベチロメ、ＢＣＴ３０４、ＺＹＴ１、ＭＢ－０７８１またはエプロチロームである、ＡＳＫ１阻害剤が、セロンセルチブである、ＡＣＣ阻害剤が、フィルソコスタットである、インテグリンアンタゴニストが、α５β１阻害剤または汎インテグリン阻害剤である、またはＦＸＲアゴニストが、シロフェクソルである、実施形態２１２の医薬組成物。
２１４．肝臓障害、脂質代謝異常、異常リポタンパク血症、腎疾患、グルコース代謝の障害、脂質代謝の障害、糖質代謝の障害、心血管疾患、血管疾患、メタボリックシンドローム、メタボリックシンドロームに伴う合併症、ＰＰＡＲ関連障害、敗血症、血栓障害、肥満、糖尿病性腎症、糖尿病性網膜症、アテローム性動脈硬化、膵臓炎、脳血管疾患、血管新生に関連する障害、高血圧、がん、炎症、炎症性疾患、神経変性疾患、自己免疫疾患、腫瘍性疾患、筋萎縮、胆汁鬱滞、ミトコンドリアの機能不全、眼疾患、リソソーム蓄積症、腎臓病もしくは勃起不全を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２１５．肝臓障害が、肝臓細胞の病理的な破壊、炎症、変性、アポトーシスまたは増殖を含む、実施形態２１４の方法。
２１６．肝臓障害が、肝線維症、脂肪肝疾患、非アルコール性脂肪性肝疾患（ＮＡＦＬＤ）または非アルコール性脂肪性肝炎（ＮＡＳＨ）である、実施形態２１４の方法。
２１７．脂質代謝異常が、高脂血症であること、または対象の血漿もしくは血清中の高密度リポタンパク質コレステロール（ＨＤＬ－Ｃ）の濃度が異常に低いことである、実施形態２１４の方法。
２１８．高脂血症が、高コレステロール血症、家族性高コレステロール血症、高トリグリセリド血症または家族性複合型高脂血症である、実施形態２１７の方法。
２１９．高脂血症が、対象の血漿もしくは血清中のリポタンパク質リパーゼレベルまたは活性の異常低下または不足、あるいは対象の血漿もしくは血清中のケトン体、リポタンパク質（ａ）コレステロール（Ｌｐ（ａ）－Ｃ）、低密度リポタンパク質（ＬＤＬ）、超低密度リポタンパク質コレステロール（ＶＬＤＬ－Ｃ）または非エステル化脂肪酸の異常に高い濃度を特徴とする、実施形態２１７の方法。
２２０．リポタンパク質リパーゼレベルもしくは活性の低下または不足が、リポタンパク質リパーゼをコードする遺伝子の変異の結果である、実施形態２１９の方法。
２２１．異常リポタンパク血症が、対象の血漿または血清中の異常に高い濃度のＬＤＬ、アポリポタンパク質（ａ）もしくはＶＬＤＬ、または対象の血漿または血清中の異常に低い濃度の高密度リポタンパク質（ＨＤＬ）もしくはリポタンパク質リパーゼを特徴とする、実施形態２１４の方法。
２２２．リポタンパク質リパーゼの濃度が異常に低いことが、リポタンパク質リパーゼ変異、低アルファリポタンパク血症、糖尿病に伴うリポタンパク質異常、肥満に伴うリポタンパク質異常、アルツハイマー病に伴うリポタンパク質異常または家族性複合型高脂血症に関連する、実施形態２２１の方法。
２２３．腎疾患が、糸球体疾患、細管疾患、尿細管間質疾患、急性または急速進行性の腎不全、慢性腎不全、腎結石または腫瘍である、実施形態２１４の方法。
２２４．糸球体疾患が、急性糸球体腎炎、慢性糸球体腎炎、迅速進行性糸球体腎炎、ネフローゼ症候群、限局性増殖性糸球体腎炎、全身性疾患に伴う糸球体病変、グッドパスチャー症候群、多発性骨髄腫、糖尿病、新生物形成、鎌状赤血球症または慢性炎症性疾患である；細管疾患が、急性尿細管壊死、急性腎不全、多発性嚢胞腎疾患、髄質海綿腎、髄質嚢胞性疾患、腎性糖尿病または腎尿細管アシドーシスである；尿細管間質疾患が、腎盂腎炎、薬物もしくは毒素誘発性尿細管間質性腎炎、高カルシウム腎症または低カリウム性腎症である；または腫瘍が、腎細胞癌または腎芽腫である、実施形態２２３の方法。
２２５．全身性疾患に伴う糸球体病変が、全身性エリテマトーデスである、実施形態２２４の方法。
２２６．腎疾患が、高血圧、腎硬化症、微小血管障害性溶血性貧血、アテローム塞栓性腎疾患、びまん性皮質壊死または腎塞栓である、実施形態２１４の方法。
２２７．高血圧が、本態性高血圧、高血圧、高血圧、悪性高血圧、二次性高血圧または白衣高血圧である、実施形態２２６の方法。
２２８．グルコース代謝の障害が、耐糖能異常；インスリン抵抗性；インスリン抵抗性関連乳がん、結腸または前立腺がん；糖尿病；膵臓炎；高血圧；多嚢胞性卵巣疾患；あるいは対象の血漿もしくは血清における異常に高い濃度の血中インスリンまたはグルコースである、実施形態２１４の方法。
２２９．糖尿病が、非インスリン依存性糖尿病（ＮＩＤＤＭ）、インスリン依存性糖尿病（ＩＤＤＭ）、妊娠糖尿病（ＧＤＭ）または若年発症成人型糖尿病（ＭＯＤＹ）である、実施形態２２８の方法。
２３０．血管疾患または心血管疾患が、末梢血管疾患、冠状動脈性心疾患、脳卒中、再狭窄、動脈硬化、虚血、内皮機能不全、虚血－再灌流損傷、心筋梗塞または脳梗塞である、実施形態２１４の方法。
２３１．ＰＰＡＲ関連障害が、関節リウマチ、多発性硬化症、乾癬、炎症性腸疾患、乳がん、結腸がんまたは前立腺がんである、実施形態２１４の方法。
２３２．ＰＰＡＲ関連障害が、血管疾患、筋疾患、脱髄疾患、筋肉構造障害、神経活性化障害、筋肉疲労障害、筋肉量障害、ミトコンドリア疾患、ミトコンドリアの機能不全、ベータ酸化疾患または代謝性疾患である、実施形態２１４の方法。
２３３．筋疾患が、筋ジストロフィー疾患である；脱髄疾患が、多発性硬化症、シャルコー－マリー－トゥース病、ペリツェウス－メルツバッハー病、脳脊髄炎、視神経脊髄炎、副腎白質ジストロフィーまたはギランバレー症候群である；筋肉構造障害が、ベスレムミオパチー、セントラルコア病、先天性筋線維不均等症、遠位筋ジストロフィー（ＭＤ）、デュシェンヌ型およびベッカー型ＭＤ、エメリー－ドレイフス型ＭＤ、顔面肩甲上腕型ＭＤ、ヒアリン体ミオパチー、肢帯型ＭＤ、筋ナトリウムチャネル障害、筋緊張性軟骨形成異常、筋強直性ジストロフィー、筋細管ミオパチー、ネマリン小体疾患、眼咽頭型ＭＤまたは腹圧性尿失禁である；神経活性化障害が、筋萎縮性側索硬化症、シャルコー－マリー－トゥース病、ギラン－バレー症候群、ランバート－イートン症候群、多発性硬化症、重症筋無力症、神経病変、末梢神経障害、脊髄性筋萎縮症、遅発性尺骨神経麻痺または毒性筋神経障害である；筋肉疲労障害が、慢性疲労症候群、糖尿病（Ｉ型またはＩＩ型）、糖原病、線維筋痛症、フリードライヒ運動失調症、間欠性跛行、脂質蓄積性ミオパチー、ＭＥＬＡＳ（ミトコンドリア脳症、乳酸アシド－シスおよび脳卒中様エピソード）症候群、ムコ多糖症、ポンペ病または甲状腺中毒性ミオパチーである；筋肉量障害が、悪液質、軟骨退化、脳性麻痺、コンパートメント症候群、重症疾患ミオパチー、封入体筋炎、筋萎縮症（廃用性）、サルコペニア、ステロイドミオパチーまたは全身性エリテマトーデスである；ミトコンドリア疾患が、アルパーズ疾患、慢性進行性外眼筋麻痺（ＣＰＥＯ）、カーンズ－セイラ症候群（ＫＳＳ）、レーベル遺伝性視神経障害（ＬＨＯＮ）、ＭＥＬＡＳ、ミオクロニーてんかんおよび赤色ぼろ線維疾患（ＭＥＲＲＦ）、神経原性筋力低下（ＮＡＲＰ）、運動失調症、網膜色素変性、ピアソン症候群、ミトコンドリアの機能不全またはミトコンドリアの機能喪失である；ベータ酸化疾患が、全身性カルニチン輸送体、カルニチンパルミトイルトランスフェラーゼ（ＣＰＴ）ＩＩ欠損症、極長鎖アシル－ＣｏＡデヒドロゲナーゼ（ＬＣＨＡＤまたはＶＬＣＡＤ）欠損症、三頭酵素欠損症、中鎖アシル－ＣｏＡデヒドロゲナーゼ（ＭＣＡＤ）欠損症、短鎖アシル－ＣｏＡデヒドロゲナーゼ（ＳＣＡＤ）欠損症またはβ－酸化のリボフラビン応答性障害（ＲＲ－ＭＡＤＤ）である；または代謝性疾患が、高脂血症、脂質代謝異常、高コレステロール血症、高トリグリセリド血症、ＨＤＬ低コレステロール血症、ＬＤＬ高コレステロール血症、ＨＬＤ非コレステロール血症、ＶＬＤＬ高タンパク血症、異常リポタンパク血症、アポリポタンパク質Ａ－Ｉ低タンパク血症、アテローム性動脈硬化、動脈硬化の疾患、心血管系の疾患、脳血管疾患、末梢循環器系疾患、メタボリックシンドローム、症候群Ｘ、肥満、糖尿病、Ｉ型糖尿病、ＩＩ型糖尿病、高血糖症、インスリン抵抗性、耐糖能異常、高インスリン症、糖尿病合併症、心不全、心筋梗塞、心筋症、高血圧、非アルコール性脂肪性肝疾患（ＮＡＦＬＤ）、非アルコール性脂肪性肝炎（ＮＡＳＨ）、血栓、アルツハイマー病、神経変性疾患、脱髄疾患、多発性硬化症、副腎白質ジストロフィー、皮膚炎、乾癬、ざ瘡、皮膚老化、多毛症、炎症、関節炎、喘息、過敏性腸症候群、潰瘍性大腸炎、クローン病または膵臓炎である、実施形態２３２の方法。
２３４．筋ジストロフィー疾患が、デュシェンヌ型筋ジストロフィー、ベッカー型筋ジストロフィー、肢帯型筋ジストロフィー、先天性筋ジストロフィー、顔面肩甲上腕型筋ジストロフィー、筋強直性ジストロフィー、眼咽頭型筋ジストロフィー、遠位筋ジストロフィーまたはエメリー－ドレフュス型筋ジストロフィーである、実施形態２３３の方法。
２３５．ＰＰＡＲ関連障害が、対象の血漿または血清中の、異常に低い濃度のＨＤＬ、異常に低い濃度のアポリポタンパク質Ａ－Ｉ（アポＡ－Ｉ）、異常に高い濃度のＶＬＤＬ－Ｃ、異常に高い濃度の低密度リポタンパク質コレステロール（ＬＤＬ－Ｃ）、異常に高い濃度のトリグリセリド、異常に高い濃度のアポリポタンパク質Ｂ（アポＢ）、異常に高い濃度のアポリポタンパク質Ｃ－ＩＩＩ（アポＣ－ＩＩＩ）またはリポタンパク質リパーゼ活性に対するヘパリン投与後の肝リパーゼの異常に低い比である、実施形態２１４の方法。
２３６．ＰＰＡＲ関連障害が、対象のリンパ液または脳脊髄液中の異常に高い濃度のＨＤＬまたは異常に低濃度のアポＡ－Ｉである、実施形態２１４の方法。
２３７．肥満が腹部肥満である、実施形態２１４の方法。
２３８．脳血管疾患が脳虚血である、実施形態２１４の方法。
２３９．血管新生に関連する障害が、網膜症または糖尿病である、実施形態２１４の方法。
２４０．がんが、ヒト肉腫またはヒト癌である、実施形態２１４の方法。
２４１．がんが、線維肉腫、粘液肉腫、脂肪肉腫、軟骨肉腫、骨原性肉種、脊索腫、血管肉腫、内皮肉腫、リンパ管肉腫、リンパ管内皮肉腫、滑膜腫、中皮腫、ユーイング腫瘍、平滑筋肉腫、横紋筋肉腫、結腸癌、膵臓がん、骨がん、乳がん、卵巣がん、前立腺がん、食道がん、口内がん、鼻腔がん、扁平上皮癌、基底細胞癌、腺癌、汗腺癌、脂腺癌、乳頭状癌、乳頭腺癌、嚢胞腺癌、髄様癌、気管支原性癌、腎細胞癌、肝細胞腫、胆管癌、絨毛癌、精上皮腫、胎生期癌、ウィルムス腫瘍、子宮頚がん、子宮がん、睾丸腫瘍、肺癌、小細胞肺癌、膀胱癌、上皮性癌、神経膠腫、星状細胞腫、髄芽腫、頭蓋咽頭腫、上衣腫、松果体腫、血管芽腫、聴神経鞘腫、乏突起神経膠腫、髄膜腫、皮膚がん、黒色腫、神経芽細胞腫、網膜芽細胞腫、白血病、急性Ｂ細胞リンパ芽球性白血病、急性Ｔ細胞リンパ芽球性白血病、急性前骨髄球性白血病、急性単芽球性白血病、急性赤白血病性白血病、急性巨核芽球性白血病、急性骨髄単球性白血病、急性非リンパ性白血病、急性未分化白血病、慢性骨髄性白血病、有毛細胞白血病、リンパ芽球性白血病、骨髄性白血病、リンパ性白血病、骨髄性白血病、真性多血症、多発性骨髄腫、リンパ腫、ホジキン病、非ホジキンリンパ腫、ワルデンシュトレームマクログロブリン血症または重鎖病である、実施形態２１４の方法。
２４２．白血病が、急性または慢性リンパ芽球性白血病、骨髄性白血病、リンパ性白血病、リンパ性白血病または骨髄性白血病である、実施形態２４１の方法。
２４３．骨髄性白血病が、急性であり、骨髄芽球性白血病、前骨髄球性白血病、骨髄単球性白血病、単球性白血病または赤白血病である、実施形態２４２の方法。
２４４．リンパ腫が、ホジキンリンパ腫または非ホジキンリンパ腫である、実施形態２４２の方法。
２４５．炎症性疾患が、多発性硬化症、関節の慢性炎症性障害、関節炎、呼吸窮迫症候群、炎症性腸疾患、炎症性肺障害、炎症性障害、歯肉の炎症性障害、結核、ハンセン病、腎臓の炎症性疾患、皮膚の炎症性障害、中枢神経系の炎症性疾患、全身性エリテマトーデス（ＳＬＥ）または心臓の炎症性疾患である、実施形態２１４の方法。
２４６．関節炎が、関節リウマチまたは骨関節炎である；炎症性腸疾患が、回腸炎、潰瘍性大腸炎またはクローン病である；炎症性肺障害が、喘息または慢性閉塞性気道疾患である；眼の炎症性障害が、角膜ジストロフィー、トラコーマ、オンコセルカ症、ぶどう膜炎、交感性眼炎または眼内炎である；歯肉の炎症性障害が、歯周炎または歯ぎん炎である；腎臓の炎症性疾患が、糸球体腎炎またはネフローゼである；皮膚の炎症性障害が、ざ瘡、硬化性皮膚炎、乾癬、湿疹、光老化またはしわである；中枢神経系の炎症性疾患が、ＡＩＤＳ関連神経変性、脳卒中、神経外傷、アルツハイマー病、脳脊髄炎またはウイルス性もしくは自己免疫性脳炎である；または心臓の炎症性疾患が、心筋症である、実施形態２４５の方法。
２４７．神経変性疾患が、アルツハイマー病またはハンチントン病である、実施形態２１４の方法。
２４８．自己免疫疾患が、免疫複合性血管炎、全身性ループスまたはエリトマトーデスである、実施形態２１４の方法。
２４９．腫瘍性疾患が発がんである、実施形態２１４の方法。
２５０．胆汁鬱滞が、肝内胆汁鬱滞性疾患または肝外胆汁鬱滞性疾患である、実施形態２１４の方法。
２５１．肝内胆汁鬱滞性疾患が、原発性胆汁性胆管炎（ＰＢＣ）、原発性硬化性胆管炎（ＰＳＣ）、進行性家族性肝内胆汁鬱滞症（ＰＦＩＣ）またはアラジール症候群（ＡＳ）である、実施形態２５０の方法。
２５２．眼疾患が、ドライアイ、マイボーム腺機能不全、角結膜上皮障害、角膜上皮障害または角膜潰瘍である、実施形態２１４の方法。
２５３．リソソーム貯蔵障害が、神経セロイドリポフスチン症、アルツハイマー病、ハンチントン病、筋萎縮性脊髄側索硬化症（ＡＬＳ）、パーキンソン病、多系統萎縮症（ＭＳＡ）、進行性核上麻痺（ＰＳＰ）、大脳皮質基底核変性症（ＣＢＤ）、レビー小体による認知症（ＤＬＢ）、オートファジー経路の障害、ティーサックス病、ファブリー病、ニーマンピック病、ゴーシェ病、ハンター症候群、アルファ－マンノシドーシス、アスパルチルグルコサミン尿症、コレステロールエステル貯蔵病、慢性ヘキソサミニダーゼＡ欠損症、シスチン症、ダノン病、ファーバー病、フコイドーシス、ガラクトシアリドーシスまたはバッテン病である、実施形態２１４の方法。
２５４．腎臓病が、腎虚血再灌流損傷である、実施形態２１４の方法。
２５５．勃起不全が、神経、動脈、平滑筋もしくは線維組織への損傷；糖尿病；腎臓病；アルコール依存症；多発性硬化症；アテローム性動脈硬化；血管疾患；または神経学的疾患に起因する、実施形態２１４の方法。
２５６．脂質異常症、高脂血症、高リポタンパク血症、高コレステロール血症、高トリグリセリド血症もしくは脂質代謝異常を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２５７．高コレステロール血症が、ホモ接合性家族性高コレステロール血症である、実施形態２５６の方法。
２５８．対象の血漿または血清において、異常に高い濃度の高低密度リポタンパク質（ＬＤＬ）、アポリポタンパク質Ｂ（アポＢ）、リポタンパク質（ａ）（Ｌｐ（ａ））、アポリポタンパク質（ａ）、もしくは超低密度リポタンパク質（ＶＬＤＬ）を有する対象を処置する、または対象が異常に高い濃度の上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２５９．対象の血漿または血清において、異常に低い濃度の高密度リポタンパク質（ＨＤＬ）を有する対象を処置する、または対象が異常に低い濃度の上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６０．対象の血漿または血清において、リポタンパク質リパーゼ濃度もしくは活性の異常低下または不足を有する対象を処置する、または対象が上記を有するのを予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６１．リポタンパク質リパーゼレベルもしくは活性の低下または不足が、リポタンパク質リパーゼをコードする遺伝子の変異の結果である、実施形態２６０の方法。
２６２．低アルファリポタンパク血症、糖尿病に伴うリポタンパク質異常、肥満に伴うリポタンパク質異常、アルツハイマー病に関連するリポタンパク質異常もしくは家族性複合型高脂血症を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６３．対象の血漿または血清中の、異常に高い濃度のトリグリセリド、低密度リポタンパク質コレステロール（ＬＤＬ－Ｃ）、超低密度リポタンパク質コレステロール（ＶＬＤＬ－Ｃ）、非高密度リポタンパク質コレステロール（非ＨＤＬ－Ｃ）、リポタンパク質（ａ）（Ｌｐ（ａ））、アポリポタンパク質Ｂ、ＨＤＬ／（ＶＬＤＬ＋ＬＤＬ）比、アポリポタンパク質Ｃ－ＩＩまたはアポリポタンパク質Ｃ－ＩＩＩを低下させる方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６４．対象の血漿または血清中の、高密度リポタンパク質（ＨＤＬ）関連タンパク質、ＨＤＬ－コレステロール、アポリポタンパク質Ａ－Ｉまたはアポリポタンパク質Ｅの異常に低い濃度を向上させる方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６５．ＨＤＬ関連タンパク質が、アポリポタンパク質Ａ－Ｉ（アポＡ－Ｉ）、アポリポタンパク質Ａ－ＩＩ（アポＡ－ＩＩ）、アポリポタンパク質Ａ－ＩＶ（アポＡ－ＩＶ）またはアポリポタンパク質Ｅ（アポＥ）である、実施形態２６４の方法。
２６６．対象の血漿または血清に由来するトリグリセリドのクリアランスを促進する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６７．対象における、異常に低いグルコース代謝または脂質代謝を向上させる方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２６８．異常に低いグルコース代謝を向上させる方法により、対象のインスリン感度または酸素消費が増大するか、あるいは対象の血漿または血清における血中インスリン、血糖もしくは糖化ヘモグロビンが低下する、実施形態２６７の方法。
２６９．異常に低い脂質代謝を向上させる方法が、対象の血漿もしくは血清における、ＬＤＬまたは遊離トリグリセリドの濃度を低下させるか、またはけん化されたもしくはけん化されていない脂肪酸合成を阻害する、実施形態２６７の方法。
２７０．炎症、全身性エリテマトーデス、ループス腎炎もしくは関節炎から選択される疾患の症状を処置または予防する方法であって、それを必要とする対象に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２７１．関節炎が、アジュバント関節炎またはＩＩ型コラーゲン誘発性関節炎である、実施形態２７０の方法。
２７２．症状が、腎炎、腎不全または腎機能低下である、実施形態２７０の方法。
２７３．家畜における肉の脂肪含有率を低下させる方法であって、家畜に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２７４．家禽卵のコレステロール含有率を低下させる方法であって、家禽の種に、有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグを投与するステップを含む、方法。
２７５．急性腎臓損傷（ＡＫＩ）を有するか、またはＡＫＩのリスクにある対象を処置する方法であって、対象に、（ｉ）有効量の実施形態１～２０７のいずれか１つの化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、あるいは（ｉｉ）実施形態２１０または実施形態２１１の医薬組成物を投与するステップを含む、方法。
２７６．（ｉ）化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、あるいは（ｉｉ）医薬組成物が静脈内に投与される、実施形態２７５の方法であって、場合により、必要に応じて３日間、１日１回、静脈内投与するステップを含む、方法。
２７７．（ｉ）化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、あるいは（ｉｉ）医薬組成物が経口投与される、実施形態２７５の方法。
２７８．ＡＫＩが、敗血症に関係するＡＫＩである、実施形態２７５～２７７のいずれか１つの方法。
２７９．ＡＫＩが、虚血／再灌流ＡＫＩである、実施形態２７５～２７７のいずれか１つの方法。
２８０．ＡＫＩが、急性間質性腎炎に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８１．ＡＫＩが、糸球体腎疾患に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８２．ＡＫＩが、血管炎性腎疾患に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８３．ＡＫＩが、虚血に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８４．ＡＫＩが、毒性傷害に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８５．ＡＫＩが、前腎性高窒素血症に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８６．ＡＫＩが、急性腎後性閉塞性（destructive）腎障害に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８７．ＡＫＩが、糖尿病に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８８．ＡＫＩが、根本的な腎不全に起因する、実施形態２７５～２７７のいずれか１つの方法。
２８９．ＡＫＩが、腎炎症候群に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９０．ＡＫＩが、アテローム性動脈硬化疾患に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９１．ＡＫＩが、低血圧に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９２．ＡＫＩが、低酸素症に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９３．ＡＫＩが、ミオグロビン尿症－血尿に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９４．ＡＫＩが、肝疾患に起因する、実施形態２７５～２７７のいずれか１つの方法。
２９５．ＡＫＩが、ウイルス感染に続発し、場合により、ウイルス感染がＣＯＶＩＤ－１９である、実施形態２７５～２７７のいずれか１つの方法。
２９６．対象がウイルス感染を有しており、場合により、ウイルス感染がＣＯＶＩＤ－１９である、実施形態２９５の方法。
２９７．対象が敗血症を有する、２７５～２７８の方法。
２９８．敗血症がグラム陰性菌感染に伴う、実施形態２９６の方法。
２９９．対象が腹腔内腔感染を有する、実施形態２９７または実施形態２９８の方法。
３００．対象が尿性敗血症を有する、実施形態２９７または実施形態２９８の方法。
３０１．対象が老年者である、実施形態２７５～３００のいずれか１つの方法。
３０２．対象が手術患者である、実施形態２７５～３０１のいずれか１つの方法。
３０３．手術患者が、心臓血管手術を受け、場合により、この手術が、冠状動脈バイパス移植（ＣＡＢＧ）手術および／または心臓弁手術である、実施形態３０２の方法。
３０４．対象が妊婦である、実施形態２７５～３００のいずれか１つの方法。
３０５．対象が腎毒性剤に曝露されてきた、実施形態２７５～３０４のいずれか１つの方法。
３０６．腎毒性剤が、シスプラチン、ゲンタマイシン、セファロリジン、シクロスポリン、アンホテリシン、四塩化炭素、トリクロロエチレン、ジクロロアセチレンまたはそれらの組合せを含む、実施形態３０５の方法。
３０７．対象がＡＫＩを有する、実施形態２７５～３０６のいずれか１つの方法。
３０８．有効量が、ＡＫＩの重症度を低下させるのに有効である、実施形態３０７の方法。
３０９．対象がＡＫＩのリスクにある、実施形態２７５～３０６のいずれか１つの方法。
３１０．対象が、場合により、冠状動脈バイパス移植（ＣＡＢＧ）手術および／または心臓弁手術である心臓血管手術の後に、ＡＫＩのリスクにある、実施形態２７５～３０６のいずれか１つの方法。
３１１．有効量が、対象がＡＫＩを発症する可能性を低減するのに有効な、実施形態３０９または実施形態３１０の方法。
３１２．有効量が、ＡＫＩの発生を遅延させるのに有効な、実施形態３０９～３１１のいずれか１つの方法。
３１３．有効量が、ＡＫＩを予防するのに有効な、実施形態３０９～３１１のいずれか１つの方法。
３１４．対象がＡＫＩを発症する場合、有効量は、ＡＫＩの重症度を低下させるのに有効な、実施形態３０９～３１１のいずれか１つの方法。
３１５．対象が、化合物、または該化合物の薬学的に許容される塩、溶媒和物、エステル、アミドもしくはプロドラッグ、あるいは医薬組成物を投与する前に、１～４のＳＯＦＡスコアを有する、実施形態２７５～３１４のいずれか１つの方法。
３１６．対象が、投与前に２～４のＳＯＦＡスコアを有する、実施形態３１５の方法。
３１７．対象が、投与前に１のＳＯＦＡスコアを有する、実施形態３１５の方法。
３１８．対象が、投与前に２のＳＯＦＡスコアを有する、実施形態３１５の方法。
３１９．対象が、投与前に３のＳＯＦＡスコアを有する、実施形態３１５の方法。
３２０．対象が、投与前に４のＳＯＦＡスコアを有する、実施形態３１５の方法。
３２１．対象が、投与前に、＞０．６の内毒素活性レベルを有する、実施形態２７５～３２０のいずれか１つの方法。
３２２．有効量が、対象の内毒素活性レベルを低下させるのに有効な、実施形態２７５～３２１のいずれか１つの方法。

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
197. A compound selected from the compounds shown in Table 1, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
198. A compound selected from the compounds shown in Table 2, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
199. A compound selected from the compounds shown in Table 3, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
200. A compound selected from the compounds shown in Table 4, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
201. A compound selected from the compounds shown in Table 5, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
202. A compound selected from the compounds shown in Table 6, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
203. A compound selected from the compounds shown in Table 7, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
204. A compound selected from the compounds shown in Table 8, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
205. A compound selected from the compounds shown in Table 9, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
206. A compound selected from the compounds shown in Table 10, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
207. A compound selected from the compounds shown in Table 11, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
208. A compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt thereof.
209. A pharmaceutically acceptable salt of a compound of any one of embodiments 1-207 that is an alkali metal salt, optionally a sodium or potassium salt.
210. A pharmaceutical composition comprising a compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, and a pharmaceutically acceptable carrier or vehicle. thing.
211. The pharmaceutical composition of embodiment 210 further comprising a second therapeutically active agent.
212. The second therapeutically active agent may be a lipid-lowering drug, a statin, a cholesterol absorption inhibitor, an antibody against PCSK9, siRNA PCSK9, an anti-fibrotic agent, a thyroid hormone, a selective thyroid receptor-β agonist, an apoptotic signal-regulated kinase 1 ( ASK1) inhibitor, an acetyl-CoA carboxylase (ACC) inhibitor, an integrin antagonist, or a non-steroidal farnesoid X receptor (FXR) agonist.
213. The lipid lowering drug is gemfibrozil, fenofibrate, bezafibrate, clofibrate, ciprofibrate, clinofibrate, etofylline, pyrifibrate, simfibrate, tocofibrate or pemafibrate, the statin is atorvastatin, simvastatin, pravastatin, rosuvastatin , fluvastatin, lovastatin, pitavastatin, mevastatin, davastatin, dihydrocompactin or cerivastatin, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, ezetimibe, the antibody against PCSK9 is evolocumab alirocumab, bococizumab, 1D05-IgG2, RG7652, LY3015014 or LGT-209, the siRNA PCSK9 is inclisiran, and the anti-fibrotic agent is nitazoxamide, tizoxanide or tizoxa The selective thyroid receptor-β agonist that is nidoglucuronide, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, is VK2809, MGL-3196, MGL-3745, SKL-14763 , sobetilome, BCT304, ZYT1, MB-0781 or eprotylome, the ASK1 inhibitor is selonsertib, the ACC inhibitor is filsocostat, the integrin antagonist is an α5β1 inhibitor or a pan-integrin inhibitor, or the pharmaceutical composition of embodiment 212, wherein the FXR agonist is cilofexol.
214. Liver disorder, lipid metabolism disorder, dyslipoproteinemia, renal disease, glucose metabolism disorder, lipid metabolism disorder, carbohydrate metabolism disorder, cardiovascular disease, vascular disease, metabolic syndrome, complications associated with metabolic syndrome, PPAR Related disorders, sepsis, thrombotic disorders, obesity, diabetic nephropathy, diabetic retinopathy, atherosclerosis, pancreatitis, cerebrovascular diseases, disorders related to angiogenesis, hypertension, cancer, inflammation, inflammatory diseases, A method of treating or preventing neurodegenerative disease, autoimmune disease, oncological disease, muscle atrophy, cholestasis, mitochondrial dysfunction, eye disease, lysosomal storage disease, kidney disease or erectile dysfunction, requiring the same. A method comprising administering to a subject an effective amount of a compound of any one of Embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
215. 215. The method of embodiment 214, wherein the liver injury comprises pathological destruction, inflammation, degeneration, apoptosis or proliferation of liver cells.
216. 215. The method of embodiment 214, wherein the liver disorder is liver fibrosis, fatty liver disease, nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH).
217. 215. The method of embodiment 214, wherein the lipid metabolic disorder is hyperlipidemia or an abnormally low concentration of high density lipoprotein cholesterol (HDL-C) in the plasma or serum of the subject.
218. The method of embodiment 217, wherein the hyperlipidemia is hypercholesterolemia, familial hypercholesterolemia, hypertriglyceridemia or familial combined hyperlipidemia.
219. Hyperlipidemia is an abnormal decrease or deficiency in lipoprotein lipase levels or activity in the subject's plasma or serum, or ketone bodies, lipoprotein (a) cholesterol (Lp(a)-C) in the subject's plasma or serum. , low density lipoprotein (LDL), very low density lipoprotein cholesterol (VLDL-C), or unesterified fatty acids.
220. 220. The method of embodiment 219, wherein the reduced or deficient lipoprotein lipase level or activity is the result of a mutation in the gene encoding lipoprotein lipase.
221. Dyslipoproteinemia is characterized by an abnormally high concentration of LDL, apolipoprotein (a), or VLDL in the subject's plasma or serum, or an abnormally low concentration of high-density lipoprotein (HDL) or 215. The method of embodiment 214, characterized by lipoprotein lipase.
222. Abnormally low levels of lipoprotein lipase can be caused by lipoprotein lipase mutations, hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial complex. 222. The method of embodiment 221 relating to hyperlipidemia.
223. 215. The method of embodiment 214, wherein the renal disease is glomerular disease, tubular disease, tubulointerstitial disease, acute or rapidly progressive renal failure, chronic renal failure, renal stone or tumor.
224. Glomerular disease is acute glomerulonephritis, chronic glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, focal proliferative glomerulonephritis, glomerular lesions associated with systemic disease, Goodpasture syndrome, multiple myeloma , diabetes, neoplasia, sickle cell disease or chronic inflammatory disease; tubular disease is acute tubular necrosis, acute renal failure, polycystic kidney disease, medullary cavernous kidney, medullary cystic disease, renal diabetes mellitus or renal tubular acidosis; the tubulointerstitial disease is pyelonephritis, drug- or toxin-induced tubulointerstitial nephritis, hypercalcic or hypokalemic nephropathy; or the tumor is renal cell carcinoma. or nephroblastoma.
225. 225. The method of embodiment 224, wherein the glomerular pathology associated with a systemic disease is systemic lupus erythematosus.
226. 215. The method of embodiment 214, wherein the renal disease is hypertension, nephrosclerosis, microangiopathic hemolytic anemia, atheroembolic renal disease, diffuse cortical necrosis, or renal embolism.
227. 227. The method of embodiment 226, wherein the hypertension is essential hypertension, hypertension, hypertension, malignant hypertension, secondary hypertension or white coat hypertension.
228. Disorders of glucose metabolism include glucose intolerance; insulin resistance; insulin resistance-related breast, colon, or prostate cancer; diabetes; pancreatitis; hypertension; polycystic ovarian disease; or abnormally high concentrations in the subject's plasma or serum. 215. The method of embodiment 214, wherein the blood insulin or glucose of
229. The method of embodiment 228, wherein the diabetes is non-insulin dependent diabetes mellitus (NIDDM), insulin dependent diabetes mellitus (IDDM), gestational diabetes mellitus (GDM) or young onset adult diabetes mellitus (MODY).
230. Embodiments where the vascular disease or cardiovascular disease is peripheral vascular disease, coronary heart disease, stroke, restenosis, arteriosclerosis, ischemia, endothelial dysfunction, ischemia-reperfusion injury, myocardial infarction or cerebral infarction. 214 methods.
231. The method of embodiment 214, wherein the PPAR-associated disorder is rheumatoid arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, breast cancer, colon cancer, or prostate cancer.
232. The PPAR-related disorder is a vascular disease, a muscle disease, a demyelinating disease, a muscle structure disorder, a neural activation disorder, a muscle fatigue disorder, a muscle mass disorder, a mitochondrial disease, a mitochondrial dysfunction, a beta oxidation disease or a metabolic disease, The method of embodiment 214.
233. The muscle disease is a muscular dystrophic disease; the demyelinating disease is multiple sclerosis, Charcot-Marie-Tooth disease, Perisseus-Merzbacher disease, encephalomyelitis, neuromyelitis optica, adrenoleukodystrophy, or Guillain-Barre syndrome; Structural disorders include Bethlem myopathy, central core disease, congenital muscle fiber asymmetry, distal muscular dystrophy (MD), Duchenne and Becker type MD, Emery-Dreyfus type MD, facioscapulohumeral type MD, and hyaline body myopathy. , limb-girdle MD, muscle sodium channel disorder, myotonic chondrodysplasia, myotonic dystrophy, myotubular myopathy, nemaline body disease, oculopharyngeal MD, or stress urinary incontinence; Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease, Guillain-Barre syndrome, Lambert-Eaton syndrome, multiple sclerosis, myasthenia gravis, nerve lesions, peripheral neuropathy, spinal muscular atrophy, late onset ulnar nerve paralysis or toxic myoneuropathies; muscle wasting disorders may include chronic fatigue syndrome, diabetes (type I or type II), glycogen storage disease, fibromyalgia, Friedreich's ataxia, intermittent claudication, and lipids. storage myopathy, MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome, mucopolysaccharidosis, Pompe disease, or thyrotoxic myopathy; muscle mass impairment may be associated with cachexia, cartilage degeneration, cerebral palsy, compartmental syndrome, severe disease myopathy, inclusion body myositis, muscular atrophy (disuse), sarcopenia, steroid myopathy or systemic lupus erythematosus; mitochondrial disease is Alpers disease, chronic progressive external ophthalmoplegia (CPEO), Kearns disease. Sayla syndrome (KSS), Leber hereditary optic neuropathy (LHON), MELAS, myoclonic epilepsy and ragged red fiber disease (MERRF), neurogenic muscle weakness (NARP), ataxia, retinitis pigmentosa, Pearson syndrome, mitochondrial Dysfunction or loss of mitochondrial function; beta-oxidation diseases are associated with systemic carnitine transporter, carnitine palmitoyltransferase (CPT) II deficiency, very long chain acyl-CoA dehydrogenase (LCHAD or VLCAD) deficiency, trihead enzyme deficiency disease, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short-chain acyl-CoA dehydrogenase (SCAD) deficiency, or riboflavin-responsive disorder of β-oxidation (RR-MADD); bloodemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, HDL hypocholesterolemia, LDL hypercholesterolemia, HLD noncholesterolemia, VLDL hyperproteinemia, dyslipoproteinemia, apolipoprotein A - I hypoproteinemia, atherosclerosis, arteriosclerosis disease, cardiovascular disease, cerebrovascular disease, peripheral circulatory system disease, metabolic syndrome, syndrome X, obesity, diabetes, type I diabetes, type II diabetes , hyperglycemia, insulin resistance, glucose intolerance, hyperinsulinism, diabetic complications, heart failure, myocardial infarction, cardiomyopathy, hypertension, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) ), blood clots, Alzheimer's disease, neurodegenerative diseases, demyelinating diseases, multiple sclerosis, adrenoleukodystrophy, dermatitis, psoriasis, acne, skin aging, hirsutism, inflammation, arthritis, asthma, irritable bowel syndrome, ulcers 233. The method of embodiment 232, wherein the disease is genital colitis, Crohn's disease or pancreatitis.
234. The muscular dystrophic disease is Duchenne muscular dystrophy, Becker muscular dystrophy, limb-girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, or Emery-Dreyfus muscular dystrophy, The method of embodiment 233.
235. PPAR-related disorders include abnormally low concentrations of HDL, abnormally low concentrations of apolipoprotein AI (apoA-I), abnormally high concentrations of VLDL-C, and abnormally high concentrations in the subject's plasma or serum. of low-density lipoprotein cholesterol (LDL-C), abnormally high concentrations of triglycerides, abnormally high concentrations of apolipoprotein B (apoB), abnormally high concentrations of apolipoprotein C-III (apoC-III) or lipoproteins. 215. The method of embodiment 214, wherein the ratio of hepatic lipase to protein lipase activity is abnormally low after heparin administration.
236. 215. The method of embodiment 214, wherein the PPAR-related disorder is an abnormally high concentration of HDL or an abnormally low concentration of apoA-I in the lymph or cerebrospinal fluid of the subject.
237. 215. The method of embodiment 214, wherein the obesity is abdominal obesity.
238. 215. The method of embodiment 214, wherein the cerebrovascular disease is cerebral ischemia.
239. The method of embodiment 214, wherein the angiogenesis-related disorder is retinopathy or diabetes.
240. The method of embodiment 214, wherein the cancer is human sarcoma or human cancer.
241. Cancers include fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endosarcoma, lymphangiosarcoma, intralymphangiosarcoma, synovioma, mesothelioma, and Ewing tumor. , leiomyosarcoma, rhabdomyosarcoma, colon cancer, pancreatic cancer, bone cancer, breast cancer, ovarian cancer, prostate cancer, esophageal cancer, oral cancer, nasal cavity cancer, squamous cell carcinoma, basal cell carcinoma , adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, choriocarcinoma, seminoma, Embryonic cancer, Wilms tumor, cervical cancer, uterine cancer, testicular tumor, lung cancer, small cell lung cancer, bladder cancer, epithelial cancer, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependyma tumor, pinealoma, hemangioblastoma, acoustic schwannoma, oligodendroglioma, meningioma, skin cancer, melanoma, neuroblastoma, retinoblastoma, leukemia, acute B-cell lymphoblastoma leukemia, acute T-cell lymphoblastic leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocytic leukemia Leukemia, acute undifferentiated leukemia, chronic myeloid leukemia, hairy cell leukemia, lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, myeloid leukemia, polycythemia vera, multiple myeloma, lymphoma, Hodgkin's disease, The method of embodiment 214, wherein the method is non-Hodgkin's lymphoma, Waldenström's macroglobulinemia, or heavy chain disease.
242. 242. The method of embodiment 241, wherein the leukemia is acute or chronic lymphoblastic leukemia, myeloid leukemia, lymphocytic leukemia, lymphocytic leukemia or myeloid leukemia.
243. 243. The method of embodiment 242, wherein the myeloid leukemia is acute and is myeloblastic leukemia, promyelocytic leukemia, myelomonocytic leukemia, monocytic leukemia or erythroleukemia.
244. 243. The method of embodiment 242, wherein the lymphoma is Hodgkin's lymphoma or non-Hodgkin's lymphoma.
245. Inflammatory diseases include multiple sclerosis, chronic inflammatory disorders of the joints, arthritis, respiratory distress syndrome, inflammatory bowel disease, inflammatory lung disorders, inflammatory disorders, gingival inflammatory disorders, tuberculosis, leprosy, and kidney inflammation. The method of embodiment 214, wherein the method is a sexually transmitted disease, an inflammatory disorder of the skin, an inflammatory disease of the central nervous system, systemic lupus erythematosus (SLE), or an inflammatory disease of the heart.
246. The arthritis is rheumatoid arthritis or osteoarthritis; the inflammatory bowel disease is ileitis, ulcerative colitis, or Crohn's disease; the inflammatory lung disorder is asthma or chronic obstructive airway disease; ocular inflammatory disease The disorder is corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis, or endophthalmitis; the gingival inflammatory disorder is periodontitis or gingivitis; the renal inflammatory disease is glomerulonephritis or nephrosis; inflammatory disorders of the skin include acne, sclerosing dermatitis, psoriasis, eczema, photoaging, or wrinkles; inflammatory disorders of the central nervous system include AIDS-related neurodegeneration, stroke, or the cardiac inflammatory disease is cardiomyopathy.
247. The method of embodiment 214, wherein the neurodegenerative disease is Alzheimer's disease or Huntington's disease.
248. 215. The method of embodiment 214, wherein the autoimmune disease is immune complex vasculitis, systemic lupus or lupus erythematosus.
249. 215. The method of embodiment 214, wherein the neoplastic disease is carcinogenesis.
250. 215. The method of embodiment 214, wherein the cholestasis is an intrahepatic cholestatic disease or an extrahepatic cholestatic disease.
251. The intrahepatic cholestatic disease is primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), progressive familial intrahepatic cholestasis (PFIC), or Alagille syndrome (AS). Method of Form 250.
252. The method of embodiment 214, wherein the eye disease is dry eye, meibomian gland dysfunction, corneal and conjunctival epithelial disorders, corneal epithelial disorders, or corneal ulcers.
253. Lysosomal storage disorders include neuronal ceroid lipofuscinosis, Alzheimer's disease, Huntington's disease, amyotrophic spinal lateral sclerosis (ALS), Parkinson's disease, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and cerebral Corticobasal degeneration (CBD), dementia due to Lewy bodies (DLB), autophagy pathway disorders, Tea-Sachs disease, Fabry disease, Niemann-Pick disease, Gaucher disease, Hunter syndrome, alpha-mannosidosis, aspartyl The method of embodiment 214, which is glucosaminuria, cholesterol ester storage disease, chronic hexosaminidase A deficiency, cystinosis, Danon's disease, Farber's disease, fucoidosis, galactosialidosis or Batten's disease.
254. 215. The method of embodiment 214, wherein the kidney disease is renal ischemia reperfusion injury.
255. Embodiments in which the erectile dysfunction is due to damage to nerves, arteries, smooth muscle or fibrous tissue; diabetes; kidney disease; alcoholism; multiple sclerosis; atherosclerosis; vascular disease; or neurological disease. 214 methods.
256. A method for treating or preventing dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia, or abnormal lipid metabolism, the method comprising administering an effective amount to a subject in need thereof. A method comprising administering a compound of any one of Forms 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
257. 257. The method of embodiment 256, wherein the hypercholesterolemia is homozygous familial hypercholesterolemia.
258. Abnormally high concentrations of high-low-density lipoprotein (LDL), apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), apolipoprotein(a), or very low-density lipoprotein (LDL) in the subject's plasma or serum. A method of treating a subject having or preventing a subject from having abnormally high levels of density lipoprotein (VLDL), comprising administering to a subject in need thereof an effective amount of embodiments 1-207. A method comprising administering any one compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound.
259. A method of treating a subject having, or preventing a subject from having, an abnormally low concentration of high-density lipoprotein (HDL) in the subject's plasma or serum, the method comprising: administering to a subject an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.
260. A method of treating a subject having, or preventing a subject from having, an abnormally reduced or deficient lipoprotein lipase concentration or activity in the subject's plasma or serum, comprising administering to a subject in need thereof an effective amount of or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.
261. 261. The method of embodiment 260, wherein the reduced or deficient lipoprotein lipase level or activity is the result of a mutation in a gene encoding lipoprotein lipase.
262. A method for treating or preventing hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial combined hyperlipidemia, the method comprising: administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound. Method.
263. Abnormally high concentrations of triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) in the subject's plasma or serum. , lipoprotein (a) (Lp(a)), apolipoprotein B, HDL/(VLDL+LDL) ratio, apolipoprotein C-II or apolipoprotein C-III, the method comprising: , an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.
264. A method for improving abnormally low concentrations of high-density lipoprotein (HDL)-related protein, HDL-cholesterol, apolipoprotein AI or apolipoprotein E in the plasma or serum of a subject in need thereof. administering an effective amount of a compound of any one of Embodiments 1-207, or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug of the compound.
265. The HDL-related protein is apolipoprotein AI (apoA-I), apolipoprotein A-II (apoA-II), apolipoprotein A-IV (apoA-IV), or apolipoprotein E (apoE). , the method of embodiment 264.
266. A method of promoting the clearance of triglycerides from the plasma or serum of a subject, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable amount of said compound. A method comprising the step of administering a salt, solvate, ester, amide or prodrug.
267. A method of improving abnormally low glucose or lipid metabolism in a subject, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable amount of the compound. A method comprising the step of administering a salt, solvate, ester, amide or prodrug.
268. 268. The method of embodiment 267, wherein the method of improving abnormally low glucose metabolism increases insulin sensitivity or oxygen consumption in the subject, or decreases blood insulin, blood sugar, or glycated hemoglobin in the subject's plasma or serum.
269. The method of embodiment 267, wherein the method of improving abnormally low lipid metabolism reduces the concentration of LDL or free triglycerides or inhibits saponified or unsaponified fatty acid synthesis in the plasma or serum of the subject.
270. A method of treating or preventing symptoms of a disease selected from inflammation, systemic lupus erythematosus, lupus nephritis or arthritis, comprising administering to a subject in need thereof an effective amount of a compound of any one of embodiments 1-207; or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of said compound.
271. The method of embodiment 270, wherein the arthritis is adjuvant arthritis or type II collagen-induced arthritis.
272. The method of embodiment 270, wherein the condition is nephritis, renal failure or decreased renal function.
273. A method of reducing the fat content of meat in livestock, comprising: administering to the livestock an effective amount of a compound of any one of embodiments 1-207, or a pharmaceutically acceptable salt, solvate, or ester of the compound. , an amide or a prodrug.
274. A method of reducing the cholesterol content of poultry eggs, comprising: administering to a species of poultry an effective amount of a compound of any one of embodiments 1 to 207, or a pharmaceutically acceptable salt, solvate of said compound; A method comprising administering an ester, amide or prodrug.
275. A method of treating a subject having acute kidney injury (AKI) or at risk of AKI, comprising: administering to the subject: (i) an effective amount of a compound of any one of embodiments 1-207; A method comprising administering a pharmaceutically acceptable salt, solvate, ester, amide or prodrug, or (ii) the pharmaceutical composition of embodiment 210 or embodiment 211.
276. The method of embodiment 275, wherein (i) the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, or (ii) the pharmaceutical composition is administered intravenously. and optionally administering intravenously once daily for 3 days as needed.
277. The method of embodiment 275, wherein (i) the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, or (ii) the pharmaceutical composition is administered orally.
278. The method of any one of embodiments 275-277, wherein the AKI is AKI associated with sepsis.
279. The method of any one of embodiments 275-277, wherein the AKI is ischemia/reperfusion AKI.
280. The method of any one of embodiments 275-277, wherein the AKI is due to acute interstitial nephritis.
281. The method of any one of embodiments 275-277, wherein the AKI is due to a glomerulonephropathy.
282. The method of any one of embodiments 275-277, wherein the AKI is due to vasculitic kidney disease.
283. The method of any one of embodiments 275-277, wherein the AKI is due to ischemia.
284. The method of any one of embodiments 275-277, wherein the AKI is due to a toxic injury.
285. The method of any one of embodiments 275-277, wherein the AKI is due to pronephric azotemia.
286. 278. The method of any one of embodiments 275-277, wherein the AKI is due to acute postrenal destructive renal injury.
287. The method of any one of embodiments 275-277, wherein the AKI is due to diabetes.
288. The method of any one of embodiments 275-277, wherein the AKI is due to underlying renal failure.
289. The method of any one of embodiments 275-277, wherein the AKI is due to a nephritic syndrome.
290. The method of any one of embodiments 275-277, wherein the AKI is due to atherosclerotic disease.
291. The method of any one of embodiments 275-277, wherein the AKI is due to hypotension.
292. The method of any one of embodiments 275-277, wherein the AKI is due to hypoxia.
293. The method of any one of embodiments 275-277, wherein the AKI is due to myoglobinuria-hematuria.
294. The method of any one of embodiments 275-277, wherein the AKI is due to liver disease.
295. The method of any one of embodiments 275-277, wherein the AKI is secondary to a viral infection, and optionally the viral infection is COVID-19.
296. 296. The method of embodiment 295, wherein the subject has a viral infection, and optionally the viral infection is COVID-19.
297. The method of 275-278, wherein the subject has sepsis.
298. 297. The method of embodiment 296, wherein the sepsis is associated with a Gram-negative bacterial infection.
299. The method of embodiment 297 or embodiment 298, wherein the subject has an intraperitoneal infection.
300. The method of embodiment 297 or embodiment 298, wherein the subject has urinary sepsis.
301. The method of any one of embodiments 275-300, wherein the subject is an elderly person.
302. The method of any one of embodiments 275-301, wherein the subject is a surgical patient.
303. 303. The method of embodiment 302, wherein the surgical patient undergoes cardiovascular surgery, optionally where the surgery is a coronary artery bypass graft (CABG) surgery and/or a heart valve surgery.
304. The method of any one of embodiments 275-300, wherein the subject is a pregnant woman.
305. The method of any one of embodiments 275-304, wherein the subject has been exposed to a nephrotoxic agent.
306. The method of embodiment 305, wherein the nephrotoxic agent comprises cisplatin, gentamicin, cephaloridine, cyclosporin, amphotericin, carbon tetrachloride, trichlorethylene, dichloroacetylene, or a combination thereof.
307. The method of any one of embodiments 275-306, wherein the subject has AKI.
308. 308. The method of embodiment 307, wherein the effective amount is effective to reduce the severity of AKI.
309. The method of any one of embodiments 275-306, wherein the subject is at risk of AKI.
310. The method of any one of embodiments 275-306, wherein the subject is at risk for AKI after cardiovascular surgery, optionally coronary artery bypass graft (CABG) surgery and/or heart valve surgery.
311. The method of embodiment 309 or embodiment 310, wherein the effective amount is effective to reduce the likelihood that the subject will develop AKI.
312. The method of any one of embodiments 309-311, wherein the effective amount is effective to delay the occurrence of AKI.
313. The method of any one of embodiments 309-311, wherein the effective amount is effective to prevent AKI.
314. The method of any one of embodiments 309-311, wherein if the subject develops AKI, the effective amount is effective to reduce the severity of AKI.
315. Embodiment 275, wherein the subject has a SOFA score of 1 to 4 prior to administering the compound, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of the compound, or pharmaceutical composition. - Any one of 314 methods.
316. The method of embodiment 315, wherein the subject has a SOFA score of 2 to 4 prior to administration.
317. The method of embodiment 315, wherein the subject has a SOFA score of 1 prior to administration.
318. The method of embodiment 315, wherein the subject has a SOFA score of 2 prior to administration.
319. The method of embodiment 315, wherein the subject has a SOFA score of 3 prior to administration.
320. The method of embodiment 315, wherein the subject has a SOFA score of 4 prior to administration.
321. The method of any one of embodiments 275-320, wherein the subject has an endotoxin activity level of >0.6 prior to administration.
322. The method of any one of embodiments 275-321, wherein the effective amount is effective to reduce endotoxin activity levels in the subject.

8. INCORPORATION BY REFERENCE All publications, patents, patent applications and other documents cited in this application are incorporated by reference for all purposes. is herein incorporated by reference for all purposes in its entirety to the same extent as if individually indicated to be incorporated by. In the event of any conflict between the teachings of one or more references incorporated herein and the teachings of this disclosure, the teachings of this specification are intended.

Claims (47)

Compound of formula (C):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, all of which are unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy , C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
R ² is C 1 substituted by C _2-8 alkyl, C _1-8 haloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, 3-7 membered _{cycloalkyl ~8} alkyl, or C _1-6 alkyl substituted by phenyl, naphthyl or pyridyl, either unsubstituted or C _1-8 alkyl, C _1-8 haloalkyl, C _{1-8 alkyl 8} alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _2-8 alkynyl, halogen, C _2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl,
A is oxygen, sulfur or NR ⁹ and R ⁹ is hydrogen or C _1-8 alkyl;
X is a C _1-8 alkylene chain, which is unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy or hydroxyl and has 0 or 1 double bond; and
Y is C(=O), C(=N-OR ¹⁰ ), CH(OR ¹¹ ), CH=CH, C≡C or C(=CH ₂ ), and R ¹⁰ and R ¹¹ are each hydrogen or C _1-8 alkyl,
R ³ , R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkoxy, C _1-8 haloalkoxy, C _2-8 alkenyl, C _{2 ~8} alkynyl, halogen, _C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl, optionally at least one of R ³ , R ⁴ and R ⁵ is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (D):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ² are each independently hydrogen, halogen, nitro, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1-3 halogens, 1-3 halogens; C _1-8 haloalkoxy with halogen, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 alkyl substituted by 3-7 membered cycloalkyl, optionally a substituted C _6-10 aryl, an arylalkyl group having a C _6-10 aryl moiety and a C _1-8 alkyl moiety, a heterocyclic group or a heterocyclic alkyl group having a C _1-8 alkyl group;
R ³ , R ⁴ and R ⁵ at each occurrence are independently hydrogen or C _1-8 alkyl;
A is an oxygen atom, a sulfur atom or ^NR3 ,
X ¹ , X ² and Z are each independently C(=O), C(=O)NH, C(=N-OR ⁴ ), CH(OR ⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH=CH, C≡C or a bond,
Y is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (E):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹² are each independently hydrogen, halogen, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl group having 1 to 3 halogens, C _1-8 haloalkoxy group having 1 to 3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl, C _1-8 having 3-7 membered cycloalkyl substituent ₈ alkyl, or phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl group (these are halogen atoms, nitro, hydroxyl, amino, C _1-8 alkyl, C _1-8 alkoxy, 1- C _1-8 haloalkyl having 3 halogens, C _1-8 haloalkoxy having 1-3 halogens, C _2-8 alkenyl, C _2-8 alkynyl, 3-7 membered cycloalkyl group, 3- a C _1-8 alkyl group with a 7-membered cycloalkyl substituent, optionally with a substituent that is phenyl or pyridyl),
X ¹ and Z ¹ are each independently C(=O), C(=O)NH, C(=N-OR ¹⁴ ), CH(OR ¹⁵ ), NH(C=O), NHSO ₂ , SO ₂ NH, CH═CH, C≡C or a bond, R ¹⁴ and R ¹⁵ are each hydrogen or C _1-8 alkyl,
Y ¹ is C _1-8 alkylene,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (F):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is O, S or ^NR7 , R7 is hydrogen or _C1-8 alkyl,
B ¹ is CW or N, W is hydrogen or a bond, B ² is O, S or NR ⁸ , R ⁸ is hydrogen or C _1-8 alkyl,
X ¹ and X ² are each O, S, NH, NHC (=O), C (=O), C (=N-OR ⁹ ), CH (OR ¹⁰ ), C=C, C≡C or a bond and R ⁹ and R ¹⁰ are each hydrogen or C _1-8 alkyl,
Y is C _1-8 alkylene, which is unsubstituted or substituted with C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z is NH, O or S;
R ¹ is aryl (which is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl having 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) or a heterocyclic group having a 5- to 8-membered ring containing 1 to 3 heteroatoms, each heteroatom being independently nitrogen, oxygen, or sulfur; the other atoms are carbon), and optionally the benzene ring is fused to the heterocyclic ring;
R ² is C _2-8 alkyl, C _1-8 haloalkyl having 1-3 halogens, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, aryl (this is an unsubstituted or substituted by C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl with 1 to 3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen) C _1-4 alkyl, or a heterocyclic group having a 5- to 8-membered ring having 1 to 3 heteroatoms, each of which is independently nitrogen, oxygen, or sulfur; is C _1-4 alkyl,
R ³ is halogen, trifluoromethyl, C _1-8 alkyl, C _2-8 alkenyl or C _2-8 alkynyl;
R ⁴ and R ⁵ are each hydrogen, C _1-8 alkyl or C _1-8 haloalkyl having 1 to 3 halogens;
Z and R ³ are each bonded to the benzene ring, and X ² is not bonded to the benzene ring,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (G):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ and R ⁴ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ² is hydrogen;
R ³ is C _1-8 alkyl, or R ³ together with R ² forms =O or =C(R ⁷ )(R ⁸ ), and R ⁷ and R ⁸ are each , are the same or different and are hydrogen or C _1-8 alkyl,
R ⁵ and R ⁶ are each the same or different and are a hydrogen atom, C _1-8 alkyl, C _1-8 haloalkyl,
X and Y are the same or different and represent CH or N, respectively;
Z is oxygen or sulfur;
A is a 5-membered heterocyclic group which is pyrazole, thiophene, furan or pyrrole, and the heterocyclic group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C 1-8 alkyl group substituted by a _3-7 membered cycloalkyl group, C _1-8 haloalkyl, C _1-8 haloalkoxy , a C _6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a 5- or 6-membered heterocyclic group. substituted with a C _1-8 alkyl group,
B is a C _1-8 alkylene chain, which is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _{1 to 8} alkoxy, halogen, C _{1 to 8} haloalkyl or C _{1 to 8} haloalkoxy, and the alkylene group has 2 to 6 carbon atoms, the alkylene group is substituted with a double bond. In some cases, we have
q is 0, 1, 2, 3, 4 or 5,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (H):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹¹ and R ¹³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ¹² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ¹⁴ and R ¹⁵ are the same or different and each is a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ¹ is CH or N,
Z ¹ is oxygen or sulfur;
W ¹ is oxygen or CH ₂ when bond a is present, and OH when bond a is absent;
q is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (J):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ²¹ and R ²³ are each the same or different, hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; C _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group;
R ²² has hydrogen, C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl group substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl moiety and C _1-8 alkylene moiety or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent,
R ²⁴ and R ²⁵ are the same or different and are each a hydrogen atom, C _1-8 alkyl or C _1-8 haloalkyl,
X ² is CH or N,
Z ² is oxygen or sulfur;
^W2 is oxygen or _CH2 when bond a is present, and OH when bond a is absent;
r is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (K):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A is CH or nitrogen,
B is oxygen or C(R ⁸ )(R ⁹ ) when bond a is present, R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and when bond a is present If not, B is OH;
W ¹ is a bond, C(=O) or (C(R ¹⁰ )(R ¹¹ )) _m , R ¹⁰ and R ¹¹ are each independently hydrogen or a C _1-8 alkyl group, m is 1, 2 or 3;
X and Y are different from each other, each is an oxygen atom, a sulfur atom, a nitrogen atom or CR ¹² , R ¹² is hydrogen or C _1-8 alkyl,
Z ¹ is a bond, oxygen, sulfur or C(R ¹³ )(R ¹⁴ ), R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
R ¹ , R ² and R ³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ⁴ and R ⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ⁶ and R ⁷ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl or C _1-8 haloalkyl;
r is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (L):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B is oxygen when bond a is present; B is OH when bond a is absent;
^W2 is a bond, C(=O) or _CH2 ,
Z ² is oxygen or sulfur;
R ²¹ , R ²² and R ²³ are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl; _1-8 haloalkoxy; hydroxyl, nitro, C _2-8 acyl group, C _6-10 aryl or 5- or 6-membered heterocyclic group,
R ²⁴ and R ²⁵ are each independently hydrogen, C _1-8 alkyl, C _1-8 haloalkyl,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (M):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently nitrogen or CH;
X is nitrogen or CH,
Y is oxygen or sulfur;
Z is a bond, oxygen, sulfur or NR ⁵ and R ⁵ is hydrogen or C _1-8 alkyl;
R ¹ and R ² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl with 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene or a C _1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R ³ and R ⁴ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
A is a 5-membered heterocycle which is pyrazole, thiophene, furan, isoxazole, isothiazole or pyrrole, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _1-8 alkyl, 3-7 membered cycloalkyl group, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, C _1-8 alkyl having a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or 5-membered or substituted with a C _1-8 alkyl group having a 6-membered heterocyclic substituent,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _1-8 alkoxy or halogen substituent optionally, the C _1-8 alkylene has a double or triple bond,
r is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (N):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^W3 is nitrogen or CH,
Z ¹ is oxygen or sulfur;
R ¹¹ and R ¹² are each independently hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 alkoxy, C _1-8 haloalkyl, or C _1-8 haloalkoxy;
R ¹³ and R ¹⁴ are each independently hydrogen or C _1-8 alkyl;
A ¹ is a 5-membered heterocycle that is pyrazole or thiophene, and the 5-membered heterocycle is unsubstituted or halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _1-8 substituted by alkoxy, C _1-8 haloalkyl or C _1-8 haloalkoxy,
m is 2, 3 or 4;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (O):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or nitrogen;
X is NR ⁵ or CR ⁶ R ⁷ and R ⁵ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, C _{3-8 7} cycloalkyl, C _1-8 alkyl substituted by C _3-7 cycloalkyl, C 1-8 alkyl substituted by phenyl, C _2-8 acyl or C _2-8 alkenyl, R ⁶ and R each ⁷ is independently hydrogen or C _1-8 alkyl;
Y is (CR ⁸ R ⁹ ) _r , R ⁸ and R ⁹ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4, or X and Y are taken together to form CR ¹⁰ =CR ¹¹ or ethynylene, and R ¹⁰ and R ¹¹ are each independently hydrogen or C _1-8 alkyl;
G is O, S or CR ¹² R ¹³ when bond a is present, R ¹² and R ¹³ are each independently hydrogen or C _1-8 alkyl, and when bond a is absent, G is OH,
A is a 5-membered heterocyclic ring which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan or pyrrole, and the heterocyclic ring is unsubstituted or C _1-8 alkyl, C _{2 ~8} alkenyl, C _2-8 alkynyl, C 1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, _hydroxyl , nitro, C _2-8 acyl, C _6-10 aryl or 5-membered or is substituted with a 6-membered heterocyclic group,
B is a C _1-8 alkylene chain, a C _2-8 alkenylene chain, or a C _2-8 alkynylene chain, and the chain is unsubstituted or C _1-8 alkyl, C _3-7 cycloalkyl, substituted with C _1-8 alkoxy or halogen,
R ¹ and R ² are each independently hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
R ³ and R ⁴ are each independently hydrogen or C _1-8 alkyl;
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (P):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^a is O, S or CH ₂ when bond a is present; when bond a is absent, G ^a is OH;
A ^a is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, substituted by halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^a is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1a and R ^2a are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (Q):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
G ^b is O, S or CH ₂ when bond a is present, and G ^b is OH when bond a is absent;
A ^b is a 5-membered heterocyclic ring which is thiazole, oxazole or thiophene, and the 5-membered heterocyclic ring is unsubstituted or C _1-8 alkyl, C _1-8 alkoxy, substituted by halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro or C _2-8 acyl,
B ^b is a C _1-8 alkylene chain or a C _2-8 alkenylene chain,
R ^1b and R ^2b are each independently hydrogen, C _1-8 alkyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, hydroxyl, nitro, or C _2-8 acyl and
R ^3b is hydrogen or C _1-8 alkyl;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (R):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
W ¹ and W ² are each independently CH or N,
X is NR ³ or CR ⁴ R ⁵ and R ³ is C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl substituted by C _1-8 alkoxy, 3-7 membered C _1-8 alkyl substituted by cycloalkyl, C _1-8 alkyl substituted by phenyl group, C _2-8 acyl or C _2-8 alkenyl,
R ⁴ and R ⁵ are each independently hydrogen or C _1-8 alkyl;
Y is (CR ⁶ R ⁷ ) _r , R ⁶ and R ⁷ are each independently hydrogen or C _1-8 alkyl, and r is 1, 2, 3 or 4;
A is a 5- or 6-membered heterocyclic group which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, pyrrole, pyridine or pyrimidine, or a phenyl group; The phenyl group is unsubstituted or C _1-8 alkyl, 3-7 membered cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxyl, 3-7 membered cycloalkyl. C _1-8 alkyl group, C _1-8 haloalkyl, C _1-8 haloalkoxy, C _6-10 aryl, 5- or 6-membered heterocyclic group, C _6-10 aryl group substituted with a group substituted by an aralkyl group containing a _1-8 alkyl group, or a C _1-8 alkyl group substituted by a 5- or 6-membered heterocyclic group,
B is a bond or C _1-8 alkylene, and C _1-8 alkylene is unsubstituted or substituted by C _1-8 alkyl, 3-7 membered cycloalkyl group, C _1-8 alkoxy or halogen. If it is substituted and the number of carbon atoms in the alkylene chain is 2 or more, it may have a double bond or triple bond,
D is N or CH;
E is O or S;
R ¹ and R ² are each independently H, C _1-8 alkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, halogen, C _1-8 haloalkyl, C _1-8 haloalkoxy, nitro, C _2-8 acyl, C _6-10 aryl or a 5- or 6-membered heterocyclic group,
m is 0, 1, 2 or 3;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (S):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
A ¹ is a 5- or 6-membered heterocyclic group such as thiazole, oxazole, pyridine, or pyrimidine, or a phenyl group, and the 5- or 6-membered heterocyclic group or phenyl group is unsubstituted or , or substituted with C _1-8 alkyl or C _1-8 haloalkyl,
B ¹ is C _2-4 alkylene;
R ¹¹ and R ¹² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ¹³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ¹³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (T):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
B ² is C _2-4 alkylene;
R ²⁰ is C _1-8 alkyl;
R ²¹ and R ²² are each independently H, C _1-8 alkyl, halogen or C _1-8 haloalkyl;
R ²³ is C _1-8 alkyl or C _1-8 haloalkyl, and optionally the N to which R ²³ is attached is attached to the 6th position of the benzisoxazole,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl;
n is 0, 1, 2, 3 or 4). Compound of formula (U):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C _1-8 alkyl, C _3-7 cycloalkyl, C2-C8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3- C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ² has hydrogen, C _1-8 alkyl, C _2-8 alkenyl, C _1-8 alkyl with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ³ , R ⁴ , R ⁵ and R ⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
X is oxygen, sulfur or NR ⁷ and R ⁷ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety, C _{2 ~8} acyl or C _2-8 alkenyl,
Y is oxygen, sulfur, NR ⁸ or a bond, R ⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
p is 0 or 1,
A is oxygen CH ₂ , N-NH ₂ or N-OR ⁹ when bond a is present, R ⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl, an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A is OH;
When p=1, B is halogen, hydroxyl, nitro, amino, C _1-8 alkyl, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3 C 1-8 alkyl having ~7-membered cycloalkyl substituent, C _1-8 haloalkyl _{, C 1-8 alkyl} having C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, a benzene ring with or without substituents that is a C _6-10 aryl group or an aralkyl group having a C _6-10 aryl moiety and a C1-C8 alkylene moiety of 1 to 8 carbon atoms; p= If 0, it is a fused ring which is indole, benzofuran, benzisoxazole or 1,2-benziisothiazole, said fused ring has or does not have a substituent, and this substituent is
Halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 membered cycloalkyl substituent C _1-8 alkyl, C _1-8 haloalkyl, C _1-8 alkyl with C1-C8 alkoxy substituent, C _1-8 haloalkoxy group, C _2-8 acyl, C _6-10 aryl, or C ₆ an aralkyl group having _~10 aryl moieties and a C _1-8 alkylene moiety;
Y is bonded to the benzene ring of B,
(C(R ³ )(R ⁴ )) _m is bonded to the fused ring of B at its 3-position,
m is an integer from 1 to 4,
n is 0, 1, 2, 3, 4 or 5;
Y is a bond when n=0,
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (V):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R11 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ¹² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ¹³ , R ¹⁴ , R ¹⁵ and R ¹⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ¹ is oxygen, sulfur, NR ¹⁸ or a bond, R ¹⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl,
A ¹ is oxygen CH ₂ , N-NH ₂ or N-OR ¹⁹ when bond a is present, R ¹⁹ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl , an aralkyl group having a C _2-8 alkenyl or C _6-10 aryl moiety and a C _1-8 alkylene moiety, and when bond a is absent, A ¹ is OH;
Q ¹ is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
r is 1, 2, 3 or 4;
s is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (W):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
^R21 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, _C1-8 alkyl, _C3-7 cycloalkyl, C2 _- C8 alkenyl, _{C2-8 alkynyl, C1-8} alkoxy, 3-8 C _1-8 alkyl with a 7-membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _1-8 alkoxy substituent, C _1-8 haloalkoxy, C _2-8 acyl, C _{a 6-10} aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group with a C _6-10 aryl moiety and a C _1-8 alkylene moiety, or a C with a 5- or 6-membered heterocyclic substituent _1-8 alkyl group,
R ²² has hydrogen, C _1-8 alkyl, C _{2-8 alkenyl, C 1-8 alkyl} with a 3-7 membered cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkoxy substituent an aralkyl group having a C _1-8 alkyl group, a C _2-8 acyl, a C _6-10 aryl or a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
R ²³ , R ²⁴ , R ²⁵ and R ²⁶ are each independently hydrogen, C _1-8 alkyl or C _1-8 haloalkyl;
Y ² is oxygen, sulfur, NR ²⁸ or a bond, R ²⁸ is hydrogen, C _1-8 alkyl, C _1-8 haloalkyl, C _2-8 acyl or C _2-8 alkenyl;
Q ² is hydrogen, halogen, hydroxyl, nitro, amino, C _1-8 alkyl group, C _3-7 cycloalkyl, C _2-8 alkenyl, C _2-8 alkynyl, C _1-8 alkoxy, 3-7 members C _1-8 alkyl with a cycloalkyl substituent, C _1-8 haloalkyl, C _1-8 alkyl with a C _{1-8 alkoxy substituent, C 1-8 haloalkoxy} , C _2-8 acyl, C _{6-8 10} aryl or an aralkyl group having a C _6-10 aryl moiety and a C _1-8 alkylene moiety;
t is 1, 2, 3 or 4,
u is 1, 2, 3, 4 or 5;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (X):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (Y):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted with alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (Z):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
Q ¹ is CH or N,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 1 or 2,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
each R ²⁰ is independently hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
^R3 is _CH3 or _CD3 ;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). Compound of formula (AA):

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof (wherein
L is (CH ₂ ) ₅ , which is unsubstituted or substituted with one methyl group;
R ¹ is hydrogen, halogen, C _1-4 alkyl, C _1-4 haloalkyl, CN, C _1-4 alkoxy, C _1-4 haloalkoxy or C _3-6 cycloalkyl,
R ² is hydrogen, halogen, CN, C _1-4 alkyl, C _1-4 haloalkyl, C _3-6 cycloalkyl, C _1-4 alkoxy, C _1-4 haloalkoxy, S (C _1-4 alkyl) , SO ₂ (C _1-4 -alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡CR ^2A , O(CH ₂ ) _m R ^2B , NH(C _{1- 4} alkyl), N(C _1-4 alkyl) ₂ or C(O)(C _1-4 alkyl), and aryl and heteroaryl are unsubstituted or halogen, OH, CN, C _{1-4 alkyl} ). ₄ substituted by alkyl, formyl, acetyl, acetoxy or carboxy, m is 1, 2 or 3;
x is 0 or 1,
R ^2A and R ^2B are each independently C _1-4 alkyl, C _1-4 haloalkyl or C _3-6 cycloalkyl;
R ³ is C _1-4 haloalkyl, NO ₂ , CN, halogen or C(O)O (C _1-4 alkyl),
R ²⁰ is hydrogen, halogen, C _1-4 alkyl, CN or C _1-4 alkoxy;
R ^X is CH ₂ OH, COH, COOCH ₂ CONR ^X4 R ^X5 , SO ₃ H

and
R ^X4 and R ^X5 are each independently alkyl, aryl or heteroaryl, or alternatively, R ^X4 and R ^X5 are taken together with the carbon atom to which R ^X4 and R ^X5 are attached. to form a heterocycle,
R ^X6 and R ^X7 are each independently H, C _1-6 alkyl, C _2-6 alkenyl or C _2-6 alkynyl). structure:

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. structure:

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. structure:

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. structure:

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. structure

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof.

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. structure

or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt of said compound. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug of said compound, and a pharmaceutically acceptable carrier or vehicle. , pharmaceutical composition. Liver disorder, lipid metabolism disorder, dyslipoproteinemia, renal disease, glucose metabolism disorder, lipid metabolism disorder, carbohydrate metabolism disorder, cardiovascular disease, vascular disease, metabolic syndrome, complications associated with metabolic syndrome, PPAR Related disorders, sepsis, thrombotic disorders, obesity, diabetic nephropathy, diabetic retinopathy, atherosclerosis, pancreatitis, cerebrovascular diseases, disorders related to angiogenesis, hypertension, cancer, inflammation, inflammatory diseases, Claims 1 to 31 for use in the treatment or prevention of neurodegenerative diseases, autoimmune diseases, oncological diseases, muscle atrophy, cholestasis, mitochondrial dysfunction, eye diseases, lysosomal storage diseases, kidney diseases or erectile dysfunction. or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. According to any one of claims 1 to 31, for use in the treatment or prevention of dyslipidemia, hyperlipidemia, hyperlipoproteinemia, hypercholesterolemia, hypertriglyceridemia or dyslipidemia. or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. Abnormally high concentrations of high-low-density lipoprotein (LDL), apolipoprotein B (apoB), lipoprotein (a) (Lp(a)), apolipoprotein (a), or very low density in the subject's plasma or serum. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, for use in the treatment or prevention of lipoproteins (VLDL). . A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable compound, for use in the treatment or prevention of abnormally low concentrations of high density lipoprotein (HDL) in the plasma or serum of a subject. salts, solvates, esters, amides or prodrugs thereof. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable compound thereof, for use in the treatment or prevention of an abnormal decrease or deficiency in lipoprotein lipase concentration or activity in the plasma or serum of a subject. salts, solvates, esters, amides or prodrugs. Claims for use in the treatment or prevention of hypoalphalipoproteinemia, lipoprotein abnormalities associated with diabetes, lipoprotein abnormalities associated with obesity, lipoprotein abnormalities associated with Alzheimer's disease, or familial combined hyperlipidemia. A compound according to any one of Items 1 to 31, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. Abnormally high concentrations of triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) in the subject's plasma or serum. , lipoprotein (a) (Lp(a)), apolipoprotein B, HDL/(VLDL+LDL) ratio, apolipoprotein C-II or apolipoprotein C-III. or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. 32. The method of claims 1-31 for use in improving abnormally low concentrations of high-density lipoprotein (HDL)-related protein, HDL-cholesterol, apolipoprotein AI or apolipoprotein E in the plasma or serum of a subject. A compound according to any one of the preceding paragraphs, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester thereof, for use in promoting the clearance of triglycerides derived from the plasma or serum of a subject, Amide or prodrug. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester thereof, for use in improving abnormally low glucose metabolism or lipid metabolism in a subject, Amide or prodrug. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate thereof, for use in the treatment or prevention of symptoms of inflammation, systemic lupus erythematosus, lupus nephritis or arthritis. , ester, amide or prodrug. A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, for use in reducing the fat content of meat in livestock. . A compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt, solvate, ester, amide or prodrug thereof, for use in reducing the cholesterol content of poultry eggs. A method of treating a subject having or at risk for acute kidney injury (AKI), the method comprising: administering to the subject: (i) an effective amount of said compound, or said pharmaceutically acceptable salt of said compound; , or a pharmaceutically acceptable salt thereof, for use in a method comprising administering a solvate, ester, amide or prodrug. Solvates, esters, amides or prodrugs.